Blood Podcast

In this week's episode, unravelling follicular lymphoma subtypes. Researchers dissect the biological diversity of follicular lymphoma and introduce a new prognostic mode, that could change the way this B-cell neoplasm is subtyped and treated. Then, concerning stroke rate trends in sickle cell disease. A new report shows increasing rates of cerebrovascular events among people with SCD in California. Finally, procoagulant platelet activation promotes venous thrombosis. Investigators report finding procoagulant platelets in the circulation and in thrombi of patients and mice with DVT or PE. 

Featured Articles:

• Follicular lymphoma comprises germinal center–like and memory-like molecular subtypes with prognostic significance
• Rates of strokes in Californians with sickle cell disease in the post-STOP era
• Procoagulant platelet activation promotes venous thrombosis

In this week's episode we’ll learn more about how clonal hematopoiesis affects prognosis in patients with telomere biology disorders, consider recently uncovered molecular subtypes of extracutaneous juvenile xanthogranulomas, and discuss a clinical trial of the BCMA-CD3 bispecific antibody teclistamab in patients with relapsed/refractory multiple myeloma who have received previous BCMA-targeted therapy.

Featured Articles:

• Clonal landscape and clinical outcomes of telomere biology disorders: somatic rescue and cancer mutations
• Recurrent CLTC::SYK fusions and CSF1R mutations in juvenile xanthogranuloma of soft tissue
• Efficacy and safety of teclistamab in patients with relapsed/refractory multiple myeloma after BCMA-targeting therapies

In this week's podcast, we'll learn about targeting mutant calreticulin in MPNs, or myeloproliferative neoplasms. Then, it’s time to address bleeding and clotting in cancer. Results of the prospective, observational CAT-BLED study provide much needed data on the high risk of clinically relevant bleeding, and its association with all-cause mortality, among cancer patients receiving systemic therapy. Finally, we'll revisit diagnostic guidelines for familial HLH, or hemophagocytic lymphohistiocytosis. The authors present new and improved diagnostic criteria with revised clinical criteria, and guidelines on cellular and genetic diagnostic assays.

Featured Articles:

• Selective targeting of mutated calreticulin by the monoclonal antibody INCA033989 inhibits oncogenic function of MPN
• Bleeding events in patients with cancer: incidence, risk factors, and impact on prognosis in a prospective cohort study
• Diagnostic guidelines for familial hemophagocytic lymphohistiocytosis revisited

In this Review Series episode on T-Cell Lymphomas introduced by Dr. Philippe Armand we’ll hear from Drs. Laurence de Leval, Javeed Iqbal, and Enrica Marchi about their work concerning new treatment practices and insights to various t-cell lymphomas.

Click here to view the complete Review Series featured in Volume 144 Issue 18 of Blood.

In this week's episode we’ll learn more about a new risk classification scheme for use in patients with acute myeloid leukemia who are ineligible for intensive therapy, efficacy and safety of daratumumab plus chemotherapy in pediatric patients with acute lymphoblastic leukemia or lymphoblastic lymphoma, and a blood bank-compatible method for creating genetically engineered platelets with a wide range of potential uses.

Featured Articles:

• Genetic Risk Stratification and Outcomes Among Treatment-Naive Patients with AML Treated With Venetoclax and Azacitidine 
• Daratumumab in Pediatric Relapsed/Refractory Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma: DELPHINUS Study 
• Genetic Engineering of Transfusable Platelets with mRNA-Lipid Nanoparticles is Compatible with Blood Banking Practices 

In this week's episode we'll learn about new explorations in extramedullary myeloma. Then, we'll hear about the role of ruxolitinib in children with acute GvHD. Finally: yapping about YAP1 as a new treatment target in immune thrombocytopenia. 

Featured Articles:

• Spatial transcriptomics reveals profound subclonal heterogeneity and T-cell dysfunction in extramedullary myeloma
• Ruxolitinib for pediatric patients with treatment-naïve and steroid-refractory acute graft-versus-host disease: the REACH4 study
• YAP1 regulates thrombopoiesis by binding to MYH9 in immune thrombocytopenia

In this week's episode we’ll learn more about the ASCEND study, which investigated first-line asciminib in chronic phase chronic myeloid leukemia; a new risk score for myeloid neoplasm transformation in patients with clonal cytopenia of undetermined significance; and use of RHD genotyped D-positive blood transfusions in patients with sickle cell and unexpected anti-D antibodies.

Featured Articles

• Asciminib Monotherapy as Frontline Treatment of Chronic Phase Chronic Myeloid Leukaemia - Results from the ASCEND Study
• Risk Prediction for Clonal Cytopenia: Multicenter Real-World Evidence 
• Genotyped RhD+ red cells for D-positive patients with sickle cell disease with conventional RHD and unexpected anti-D 

In this week's episode we'll learn about the updated phase 3 results on fixed-dose venetoclax plus obinutuzumab in previously untreated CLL. Then, we'll hear about dual epi-immunotherapy in classical Hodgkin lymphoma. Finally we'll explore redefining risk of treatment failure in CML.

Featured Articles:

• Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized phase 3 CLL14 study
• Epigenetic agents plus anti-PD-1 reprogram the tumor microenvironment and restore antitumor efficacy in Hodgkin lymphoma
• A predictive model for therapy failure in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitor therapy

In this week's episode we’ll learn more about the role of ERG loss-of-function variants in bone marrow failure and hematological malignancies, a proposed pathway linking factor 11 activation to increased vascular permeability during inflammation, and new clinical criteria for diagnosing anemia, defining transfusion-dependence, and evaluating anemia treatment responses in patients with myelofibrosis.

Featured Articles:

• Germ line ERG haploinsufficiency defines a new syndrome with cytopenia and hematological malignancy predisposition
• Coagulation factor XI regulates endothelial cell permeability and barrier function in vitro and in vivo
• Proposals for revised International Working Group–European LeukemiaNet criteria for anemia response in myelofibrosis

In this week's episode, we'll learn about the role of a platelet-specific glycoprotein receptor in abdominal aortic aneurysm formation, the influence of TP53 mutations on outcomes for patients with 5q-deleted myelodysplastic syndrome, and a rational combination treatment intended to produce more durable responses in patients with refractory B-cell acute lymphoblastic leukemia who are treated with CAR T-cell therapy.

Featured Articles:

• Soluble glycoprotein VI predicts abdominal aortic aneurysm growth rate and is a novel therapeutic target
• Influence of TP53 gene mutations and their allelic status in myelodysplastic syndromes with isolated 5q deletion
• A phase 1 clinical trial of NKTR-255 with CD19-22 CAR T-cell therapy for refractory B-cell acute lymphoblastic leukemia

In this week's episode we'll learn about refining risk stratification in T-cell acute lymphoblastic leukemia, or ALL. After that, we'll discuss a novel gene therapy approach in severe alpha-thalassemia. Investigators describe an innovative mouse model and an effective gene therapy approach, renewing prospects for the development of novel strategies to treat this disease. Finally, we'll hear about how genomic profiling has helped identify subgroups associated with distinct clinical phenotypes and outcomes in the molecular taxonomy of myelodysplastic syndromes, or MDS.

Featured Articles 

• NGS-based stratification refines the risk stratification in T-ALL and identifies a very-high-risk subgroup of
  patients
• Use of HSC-targeted LNP to generate a mouse model of lethal α-thalassemia and treatment via lentiviral
  gene therapy
• Molecular taxonomy of myelodysplastic syndromes and its clinical implications

In this week's episode we’ll discuss a novel tripartite fusion drives treatment resistance in acute promyelocytic leukemia. In some patients with atypical APL, these novel retinoic acid receptor gene fusions result in truncation of the ligand binding domain of the retinoic acid receptor protein, resulting in non-responsiveness to treatment with all-trans retinoic acid. After that: managing immune thrombotic thrombocytopenia or iTTP without therapeutic plasma exchange, or TPE. Finally, hope for motherhood after allogeneic HCT.

Featured Articles: 

• Critical role of tripartite fusion and LBD truncation in certain RARA- and all RARG-related atypical APL
• Management of immune thrombotic thrombocytopenic purpura without therapeutic plasma exchange
• Hope for motherhood: pregnancy after allogeneic hematopoietic cell transplantation (a national multicenter study)

In this week's episode we’ll discuss the safety and efficacy of pirtobrutinib with or without rituximab in relapsed/refractory CLL; learn more about erythroid 5ALA synthesis disorders and their conditional synthetic lethal dependency on pyridoxine; and discuss how targeting PKC alpha alleviates iron overload in diabetes and hemochromatosis through the inhibition of ferroportin.

Featured Articles:

• Fixed-duration pirtobrutinib plus venetoclax with or without rituximab in relapsed/refractory CLL: Phase 1b BRUIN trial
• Murine models of erythroid 5ALA synthesis disorders and their conditional synthetic lethal dependency on pyridoxine
• Targeting PKCα alleviates iron overload in diabetes and hemochromatosis through the inhibition of ferroportin

In this week's episode we'll discuss outcomes following hematopoietic stem cell transplantation in pediatric patients with Fanconi anemia. Then, we'll learn about how new research shows that the transcription factor Foxo1, commonly associated with glucose metabolism, regulates hepcidin expression and systemic iron homeostasis. Finally, in Latin America: using clinical networks to improve outcomes in patients with acute promyelocytic leukemia. After clinical networks were established, survival and relapse rates improved substantially, highlighting the effectiveness of this unique intervention strategy in low- and middle-income countries.

Featured Articles: 

• Outcomes of hematopoietic stem cell transplantation in 813 pediatric patients with Fanconi anemia
• Foxo1 is an iron-responsive transcriptional factor regulating systemic iron homeostasis
• Clinical networking results in continuous improvement of the outcome of patients with acute promyelocytic
  leukemia

In this week's episode we’ll discuss how CD8+ T-cell differentiation and dysfunction inform treatment response in acute myeloid leukemia; learn more about the effect of ATM germline pathogenic variants on the outcomes in children with ataxia-telangiectasia and hematological malignancies; and discuss the preclinical efficacy of a potent, selective menin-KMT2A inhibitor JNJ-75276617 in KMT2A- and NPM1-altered leukemias.

Featured Articles:

• CD8+ T-cell differentiation and dysfunction inform treatment response in acute myeloid leukemia
• ATM germ line pathogenic variants affect outcomes in children with ataxia-telangiectasia and hematological
  malignancies
• Preclinical efficacy of the potent, selective menin-KMT2A inhibitor JNJ-75276617 (bleximenib) in
  KMT2A- and NPM1-altered leukemias

In this week's episode we'll discuss HA-1-targeted T-cell receptor T-cell therapy for recurrent leukemia after hematopoietic stem cell transplantation. Next, we'll learn about how 4D intravital imaging in mice reveals the key role of platelets as a source of procoagulant membranes in hemostasis. Finally, we'll hear about modifications to a common induction and maintenance treatment for treatment-naïve mantle-cell lymphoma.

Featured Articles

• HA-1–targeted T-cell receptor T-cell therapy for recurrent leukemia after hematopoietic stem cell
  transplantation
• 4D intravital imaging studies identify platelets as the predominant cellular procoagulant surface in a mouse
  hemostasis model
• Randomized study of induction with bendamustine-rituximab ± bortezomib and maintenance with
  rituximab ± lenalidomide for MCL

In this week's episode we’ll discuss the outcomes of younger patients with mantle cell lymphoma experiencing late relapse; learn more about mass spectrometry-based assessment of M-protein in peripheral blood during maintenance therapy in multiple myeloma and discuss in vivo CAR T-cell generation in non-human primates using lentiviral vectors.

Featured Articles: 

• Outcomes of younger patients with mantle cell lymphoma experiencing late relapse (>24 months): the LATE-POD study
• Mass spectrometry–based assessment of M protein in peripheral blood during maintenance therapy in
  multiple myeloma
• In vivo CAR T-cell generation in nonhuman primates using lentiviral vectors displaying a multidomain fusion ligand

Introduced by Associate Editor Dr. Thomas Ortel, this bonus episode discusses the Review Series on Factor XI, published in volume 143 issue 15 of Blood Journal. Dr. Ortel is joined by contributing authors Owen McCarty, PhD, Gili Kenet, MD, and David Gailani, MD.

Review Series Articles: 

• Introduction to a review series on factor XI
• Biology of factor XI
• Targeting factor XI and factor XIa to prevent thrombosis
• Factor XI deficiency: phenotypic age-related considerations and clinical approach towards bleeding risk assessment

In this week's episode we'll learn how cytomegalovirus infection early in life depletes preleukemic cells in a mouse model of B-cell acute lymphoblastic leukemia. After that we'll discuss new research, where GVHD targets organoid-forming bile duct stem cells in a TGF-beta-dependent manner. Conversely, a TGF-beta inhibitor protects these stem cells against GVHD and mitigates biliary dysfunction. Finally, we'll hear about the seven-year outcomes for venetoclax-ibrutinib in relapsed or refractory mantle cell lymphoma. In addition to long-term survival benefits, researchers report durable treatment-free remissions and effective retreatment in patients with MRD-negative complete responses.

Featured Articles: 

• Early-life infection depletes preleukemic cells in a mouse model of hyperdiploid B-cell acute lymphoblastic
  leukemia
• GVHD targets organoid-forming bile duct stem cells in a TGF-β–dependent manner
• Seven-year outcomes of venetoclax-ibrutinib therapy in mantle cell lymphoma: durable responses and
  treatment-free remissions

In this week's episode we'll learn about iron, HFE hemochromatosis, and infections. In this large, population-based study, both high and low levels of plasma iron and transferrin saturation were associated with increased risks of infection. Then, we'll discuss how bispecific antibodies improve CAR T-cell response in B-cell malignancies. In-vitro and in-vivo data demonstrate enhanced therapeutic efficacy when a CD20-directed bispecific antibody is given in combination with CD19-directed CAR-T cells. Finally, we'll hear about determinants of outcome in NPM1-mutated AML. In a large series of patients with NPM1-mutated AML, investigators identified several variables beyond FLT3-ITD that adversely impacted outcomes.

Featured Articles:

• Iron, hemochromatosis genotypes, and risk of infections: a cohort study of 142 188 general population individuals
• Molecular, clinical, and therapeutic determinants of outcome in NPM1-mutated AML
• CD20-bispecific antibodies improve response to CD19-CAR T cells in lymphoma in vitro and CLL in vivo models

In this week's episode we’ll discuss how immune fitness impacts response to teclistamab in relapsed/refractory multiple myeloma; learn more about a new mechanism of resistance to asciminib conferred by the BCR::ABL1 M244V mutation, and discuss the impact of hematopoietic cell transplantation on myocardial fibrosis in young patients with sickle cell disease.

Featured Articles:

• Correlation of immune fitness with response to teclistamab in relapsed/refractory multiple myeloma in MajesTEC-1
• BCR::ABL1 kinase N-lobe mutants confer moderate to high degrees of resistance to asciminib
• Impact of hematopoietic cell transplantation on myocardial fibrosis in young patients with sickle cell disease

In this week's episode we’ll discuss the safety and efficacy of decitabine in older patients with AML; learn how heme-induced loss of renovascular endothelial protein C receptor promotes chronic kidney disease in sickle mice, and discuss the outcomes of treatment with HLA-mismatched HSCT with TCRab/CD19 lymphocyte depletion or post-HSCT cyclophosphamide for inborn errors of immunity.

Featured Articles:

• Decitabine in older patients with AML: Quality of life results of the EORTC-GIMEMA-GMDS-SG randomized phase III trial 
• Heme induced loss of renovascular endothelial protein C receptor promotes chronic kidney disease in sickle mice 
• Outcomes of HLA-mismatched HSCT with TCRab/CD19 depletion or post-HSCT cyclophosphamide for inborn errors or immunity 

In this week's episode we'll discuss minimal residual disease as an intermediate clinical endpoint for multiple myeloma. Then, we'll learn about IPSS-R downstaging before transplant in MDS. Finally we'll hear about the connection between hereditary angioedema and venous thromboembolism. 

Featured Articles:

• EVIDENCE meta-analysis: evaluating minimal residual disease as an intermediate clinical endpoint for multiple myeloma 
• Does IPSS-R down-staging before transplantation improve the prognosis of patients with Myelodysplastic Neoplasms? 
• Increased risk of venous thromboembolism [or VTE] in young and middle-aged individuals with hereditary angioedema: a family study

In this week's episode we’ll discuss the safety and efficacy of acalabrutinib, venetoclax and obinutuzumab in relapsed/refractory CLL; learn more about alternative donor transplantation for severe aplastic anemia and discuss clonal relapse dynamics in acute myeloid leukemia following allogeneic hematopoietic cell transplantation.

Featured Articles: 

• Acalabrutinib, venetoclax and obinutuzumab in relapsed/refractory CLL: Final efficacy and ctDNA analysis of the CLL2-BAAG trial 
• Alternative donor transplantation for severe aplastic anemia: a comparative study of the SAAWP EBMT 
• Clonal relapse dynamics in acute myeloid leukemia following allogeneic hematopoietic cell transplantation 

In this week's episode we'll learn about the clinical benefit of complete remission with partial hematological recovery, or CRh, in patients with Acute Myeloid Leukemia (AML) treated with molecularly targeted drugs. Then we'll hear about a large cohort of patients with PNH were studied to detail PNH-related thrombotic events, unravel determinants of thrombosis, and evaluate anti-coagulation strategies. Finally, we'll see how new research shows that SOX11 expression is restricted to EBV-negative Burkitt lymphoma, and is associated with a specific genetic landscape. 

Featured Articles:

• Complete Remission with Partial Hematological Recovery as a Palliative Endpoint for Treatment of Acute Myeloid Leukemia 
• Paroxysmal nocturnal hemoglobinuria-related thrombosis in the era of novel therapies: a 2043 patient/years analysis 
• SOX11 expression is restricted to EBV-negative Burkitt lymphoma and associates with molecular genetic features 

In this week's episode we’ll discuss the mutational and transcriptional landscape of pediatric BCP lymphoblastic leukemia; learn more about the role of platelet-derived TGF-β1 in immune thrombocytopenia; and discuss the findings from a phase 3 trial of mavorixafor in WHIM syndrome.

Featured Articles:

• Mutational and transcriptional landscape of pediatric B-cell precursor lymphoblastic lymphoma 
• Platelet-derived TGF-β1 induces functional reprogramming of myeloid-derived suppressor cells in immune thrombocytopenia 
• Phase 3 randomized trial of mavorixafor, CXCR4 antagonist, in WHIM syndrome 

Introduced by Associate Editor Robert Zeiser, this Review Series focuses on the problem of immune escape by acute myeloid leukemia (AML). The series opens with a review of how AML escapes T-cell–driven elimination and then focuses on how p53 function impinges on AML recognition by immune cells. The series finishes with a summary of new approaches to tackling this major problem.

Featured Series:

• Introduction to a review series on oncogenic signaling and immune evasion in hematologic malignancies

In this week's episode we'll discuss new insights on the role of GM-CSF in establishing immune memory. The authors propose that the coordination of opposing immune memory programs, driven by GM-CSF, may be essential to efficient, yet controlled, innate immune responses. After that: Interleukin-1 inhibition in TTP. Researchers explore the potential of recombinant IL-1 receptor antagonist, anakinra, in a murine model of thrombotic thrombocytopenic purpura—an uncommon but potentially fatal disorder with limited therapeutic options. Finally, we'll learn about CAR T-cell therapy outcomes by race and ethnicity in large B-cell lymphoma. Non-Hispanic Black patients had lower rates of response and progression-free survival in axi-cel clinical trials and real-world data, raising awareness and giving further insights into potential inequitable access to care.

Featured Articles:

• GM-CSF receptor expression determines opposing innate memory phenotypes at different stages of myelopoiesis 
• Mortality, cardiac and cerebral damage reduction by IL-1 inhibition in a murine model of TTP 
• Real-World and Clinical Trial Outcomes in Large B-cell Lymphoma with Axicabtagene Ciloleucel Across Race and Ethnicity 

In this week's episode we’ll discuss the prognostic value of the Chronic Lymphocytic Leukemia International Prognostic Index in the era of targeted therapies, learn how peak ADAMTS13 activity can be used to assess ADAMTS13 conformation and risk of relapse in immune-mediated thrombotic thrombocytopenic purpura, and discuss the findings from a phase 2 trial of haploidentical bone marrow transplant in sickle cell disease.

Featured Articles

• Reassessing the Chronic Lymphocytic Leukemia International Prognostic Index in the era of targeted therapies 
• Peak ADAMTS13 activity to assess ADAMTS13 conformation and risk of relapse in immune-mediated Thrombotic Thrombocytopenic Purpura 
• An international learning collaborative phase 2 trial for haploidentical bone marrow transplant in sickle cell disease 

In this week's episode we'll discuss assessing risk profile in Wiskott-Aldrich Syndrome, or WAS. Then, we'll learn about how the loss of DNMT3A confers resistance to interferon-alpha in hematopoietic stem cells carrying the JAK2-V617F mutation. Finally, we'll explore unrelated donor selection for AML patients undergoing hematopoietic stem cell transplantation with post-transplant cyclophosphamide.

Featured Articles: 

• Wiskott-Aldrich Syndrome: A retrospective study on 577 patients defines the genotype as a predictive biomarker for disease severity and survival
• Loss of Dnmt3a increased self-renewal and resistance to pegylated interferon-alpha in JAK2-V617F-positive myeloproliferative neoplasms 
• Younger unrelated donors may be preferable over HLA match in the PTCy era: A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

In this week's episode we’ll discuss the safety and efficacy of nilotinib with or without cytarabine in Philadelphia-positive acute lymphoblastic leukemia; learn more about thrombosis risk in double heterozygous carriers of Factor V Leiden and prothrombin G20210A and discuss the utility of circulating cell-free tumor DNA in prognostic prediction in patients with relapsed/refractory multiple myeloma.

Featured Articles:

• Nilotinib with or without cytarabine for Philadelphia positive acute lymphoblastic leukemia 
• Thrombosis risk in double heterozygous carriers of Factor V Leiden and Prothrombin G20210A in FinnGen and the UK Biobank 
• ctDNA improves prognostic prediction in relapsed/refractory multiple myeloma receiving ixazomib, lenalidomide, and dexamethasone 

In this week's episode we'll learn about fitusiran prophylaxis in patients with hemophilia A or B, with or without inhibitors. Next we'll hear about new findings that heterozygous germline variants in the NBN gene that are linked to increased risk of B-cell acute lymphoblastic leukemia in children. Finally, we'll explore new insights on the histone demethylase PHF8, which has been identified as a master regulator of cell-intrinsic immune responses in acute myeloid leukemia. 

Featured Articles:

• Fitusiran prophylaxis in people with hemophilia A or B who switched from prior BPA/CFC prophylaxis: the ATLAS-PPX trial
• Germline genetic NBN variation and predisposition to B-cell acute lymphoblastic leukemia in children 
• Epigenetic control over the cell-intrinsic immune response antagonizes self-renewal in acute myeloid leukemia

In this week's episode we’ll discuss the effects of voxelotor on cerebral blood flow in pediatric sickle cell disease, learn more about venous and arterial thrombosis in patients with Vexas syndrome, and discuss differential sensitivity to tyrosine kinase inhibitors in ABL-class acute lymphoblastic leukemia. 

Featured Articles:

• The influence of voxelotor on cerebral blood flow and oxygen extraction in pediatric sickle cell disease 
• Venous and arterial thrombosis in patients with VEXAS syndrome 
• Tyrosine kinase inhibitor response of ABL-class acute lymphoblastic leukemia: The role of kinase type and SH3 domain 

In this week's podcast we'll discuss another step forward in stamping out high-risk myeloma. Then we'll hear about the plasmin-cleaved von Willebrand factor, or VWF, in microthrombosis. Finally we'll hear about new insights into the origins of sickle cell pain. 

Featured Articles:

• Daratumumab, carfilzomib, lenalidomide, and dexamethasone with tandem transplant for high-risk newly
  diagnosed myeloma
• Plasmin-cleaved von Willebrand factor as a biomarker for microvascular thrombosis
• Sickle cell disease iPSC-derived sensory neurons exhibit increased excitability and sensitization to patient
  plasma

In this week's episode we’ll discuss the utility of MRD in identifying patients with NPM1 AML who benefit from allogeneic transplant in first remission, learn more about the contribution of circulating hematopoietic stem/progenitor cell subsets to human hematopoietic hemostasis, and discuss the role of Let-7 miRNAs in regulation of BCL11A transcription and hemoglobin switching. 

Featured Articles:

• Postinduction molecular MRD identifies patients with NPM1 AML who benefit from allogeneic transplant in first remission
• let-7 miRNAs repress HIC2 to regulate BCL11A transcription and hemoglobin switching 
• Circulating Hematopoietic Stem/Progenitor Cell subsets contribute to human hematopoietic homeostasis

In this week's epside we'll learn about ADAMTS recovery after caplacizumab therapy in patients with immune thrombotic thrombocytopenic purpura. Then, we'll hear about preclinical characterization of sonrotoclax, a potential second-generation BCL2 inhibitor. Finally we'll hear about new insights into the etiology of Castleman disease where researchers describe the unusual occurrence of idiopathic multicentric Castleman disease in identical twins. 

Featured Articles: 

• ADAMTS13 recovery in acute thrombotic thrombocytopenic purpura after caplacizumab therapy
• Sonrotoclax overcomes BCL2 G101V mutation–induced venetoclax resistance in preclinical models of
  hematologic malignancy
• Single-cell landscape of idiopathic multicentric Castleman disease in identical twins

In this week's episode, we’ll discuss the findings from a study assessing responses after treatment with tisagenlecleucel [LM1] in adults with relapsed/refractory follicular lymphoma, learn more about the association between high microRNA-145 plasma levels and decreased risk of future incident venous thromboembolism, and discuss how epigenetic and immunogenetic signatures can be used in the prediction of outcomes for high-count monoclonal B lymphocytosis.

Featured Articles: 

• Durable Response After Tisagenlecleucel in Adults With Relapsed/Refractory Follicular Lymphoma: ELARA Trial Update 
• Prediction of outcomes for high-count monoclonal B lymphocytosis using an epigenetic and immunogenetic signature 
• High microRNA-145 plasma levels are associated with decreased risk of future incident venous thromboembolism: The HUNT study 

In this week's episode, we'll discuss gut microbiota exploitation by CPX-351 in acute myeloid leukemia. Then we'll learn about optimizing anti-myeloma immunity. New research shows that regulatory T cells suppress myeloma-specific immunity during autologous stem cell mobilization and transplantation. Finally we'll discuss among pediatric patients with ITP or other autoimmune cytopenias, which ones will go on to develop systemic lupus? 

Featured Articles: 

• CPX-351 exploits the gut microbiota to promote mucosal barrier function, colonization resistance, and immune homeostasis
• Regulatory T cells suppress myeloma-specific immunity during autologous stem cell mobilization and transplantation
• Antinuclear antibody–associated autoimmune cytopenia in childhood is a risk factor for systemic lupus erythematosus

In this week's episode we’ll discuss the mechanism by which Jak2V617F clonal hematopoiesis promotes arterial thrombosis, discuss how Staphylococcus aureus induces drug resistance in cancer T cells in Sézary syndrome, and learn more about the clinical and functional features of RAC2-related immunodeficiency.

Featured Articles:

• Jak2V617F clonal hematopoiesis promotes arterial thrombosis via platelet activation and cross talk
• Staphylococcus aureus induces drug resistance in cancer T cells in Sézary syndrome
• Clinical and functional spectrum of RAC2-related immunodeficiency
  

  
  

In this week's episode we'll discuss molecular mimicry in aplastic anemia, novel experiments show that antigens associated with viral infections can mimic epitopes presented on hematopoietic progenitor cells. Then, we'll learn about prophylaxis with subcutaneous emicizumab in infants with hemophilia. Finally we'll see how hydroxyurea is associated with a significant reduction in infections among children with sickle cell anemia in Uganda.

Articles featured this week:

• Virus-reactive T cells expanded in aplastic anemia eliminate hematopoietic progenitor cells by molecular
  mimicry
• Emicizumab prophylaxis in infants with hemophilia A (HAVEN 7): primary analysis of a phase 3b open-label
  trial
• Hydroxyurea reduces infections in children with sickle cell anemia in Uganda

In this bonus episode of Blood Podcast, Associate Editor, Dr. Freda Stevenson is joined by Drs. Karin Tarte, Andrea Radtke, and Leandro Cerchietti to discuss the Review Series on the influence of the tumor microenvironment on the pathogenesis of B-cell lymphomas.

Find the full review series in Blood Journal volume 143 issue 12. 

In this week's episode we’ll discuss the findings from a study assessing the utility of free light chain mass spectrometry in AL amyloidosis, learn more about distinct single-cell RNA-sequencing signatures of bone marrow T cells of AML patients in remission after an allogeneic stem cell transplant, and discuss why von Willebrand factor clearance is critical for the protective effect of ADAMTS13 in mice with sickle cell anemia.

Articles featured in this episode: 

• Clearance of VWF by hepatic macrophages is critical for the protective effect of ADAMTS13 in sickle cell anemia mice 
• Complete responses in AL amyloidosis are unequal: the impact of free light chain mass spectrometry in AL amyloidosis
• The remission status of patients with AML post-alloSCT is associated with a distinct single-cell bone marrow T-cell signature 

In this week's episode we'll discuss eculizumab in stem cell transplant-associated thrombotic microangiopathy. Then, we'll learn about reclassifying malignant monocytosis, these newly classified cases have distinct mutational and transcriptional profiles. Finally, we'll hear about targeting the tissue factor coagulation initiation complex prevents antiphospholipid antibody development.

Articles featured in this episode:

•  A prospective multi-institutional study of eculizumab to treat high-risk stem cell transplantation–associated TMA
•  Comparing malignant monocytosis across the updated WHO and ICC classifications of 2022
•  Treatment outcomes of complement protein C5 inhibition in 509 UK patients with paroxysmal nocturnal hemoglobinuria
  
  

In this week's episode we’ll learn more about rare relapse-initiating stem cells in patients with MDS or AML in complete remission post-transplantation, discuss the role of interferon α in erythropoiesis in sickle cell disease, and learn more about how TNFα promotes clonal dominance of KIT D816V+ cells in mastocytosis.

In this week's episode we'll discuss PAR2-biased signaling in thrombo-inflammation. Then, we'll learn about how hemoglobin levels are linked to survival in transfusion-dependent beta-thalassemia. Finally we'll hear about how etoposide is better than its reputation in primary HLH—hemophagocytic lymphohistiocytosis. Symptomatic patients treated with etoposide have substantially better outcomes as compared to the historical experience.

In this week's episode we’ll discuss the findings from a prospective trial of brentuximab vedotin with dacarbazine or nivolumab in older patients with classical Hodgkin lymphoma, learn more about CD20 antigen loss as a mechanism of resistance to mosunetuzumab in relapsed/refractory B-cell lymphomas, and discuss the role of trogocytosis in red blood cell antigen loss.

In this week's episode we'll discuss CAR T cells plus ibrutinib for the treatment of relapsed/refractory mantle cell lymphoma. Next, we'll learn about a new SAGA for acute myeloid leukemia. Finally, we'll hear about new evidence that oxygen delivery to tissues can become diffusion-limited during perfusion with stored blood.

In this week's episode we’ll report on the findings from a study evaluating the long-term outcomes of pulmonary embolism in children and adolescents, discuss a new mechanism for hereditary angioedema caused by a methionine-379 to lysine substitution in kininogens, and learn more about predictors of unsustained minimal residual disease negativity in multiple myeloma patients.

In this week's episode we'll discuss extended follow-up from the ZUMA-5 trial of axicabtagene ciloleucel, or axi-cel. Then we'll learn about the role of platelets in binding and clearing senescent red blood cells. Finally, we'll hear about a new risk stratification strategy for lymphomas of the central nervous system, or CNS. 

In this week's episode we’ll discuss the findings from a two-year follow-up study of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphoma, learn more about how reciprocal stabilization of coagulation factor XIII-A and -B subunits influences plasma FXIII concentration, and discuss the findings from a phase 2 study of inotuzumab ozogamicin for measurable residual disease in acute lymphoblastic leukemia in remission.

In this week’s episode, we’ll discuss the association between occupational exposure to anticancer agents in a parent and subsequent cancer in a child. Then we’ll learn about deciphering and disrupting the activation of PIEZO1 in hereditary xerocytosis. Finally, we’ll hear about the assessment of measurable residual disease, or MRD, in patients with NPM1-mutated AML, or acute myeloid leukemia, receiving venetoclax-based NON-intensive therapy.

In this week's episode we’ll discuss the findings from a prospective trial of TCRαβ/CD19-cell depleted HLA-haploidentical transplantation to treat pediatric acute leukemia, learn more about the incidence, clinical characteristics, and survival of malignancy-associated hemophagocytic lymphohistiocytosis in Sweden, and discuss the bone marrow as the primary site of thrombopoiesis. 

In this week's episode we’ll explore the role of fibrinogen polymerization in thrombosis. Then, we’ll discuss preventing CD19-negative relapse after CAR T-cell therapy in acute lymphoblastic leukemia. Finally, we’ll learn how increased levels of the RNA-binding protein FUS has been identified as an effector of hematopoietic stem cell aging. 

In this week's episode we’ll discuss the findings from a phase 2 study of CD24Fc for prevention of graft-versus-host disease, learn more about the origins of chronic active Epstein-Barr virus disease, and discuss the role of PF4 in platelet activation.

In this week's episode we'll uncover the clinical and pathological profile of a new disorder similar to VITT, or vaccine-induced thrombocytopenia and thrombosis. Then, we'll discuss real-world outcomes in patients with large B-cell lymphoma treated with tafasitamab and lenalidomide. Finally we'll learn about how advances in technology help unravel the spatial biology of bone marrow. 

In this week's episode we’ll discuss the findings from a natural history study of patients with familial platelet disorder with myeloid malignancy, learn more about the role of HEXIM1 as an essential transcription regulator in human erythropoiesis, and discuss the utility of residual disease as a predictor of relapse in CML patients stopping TKI therapy.

On today's episode we’ll discuss the prognostic significance of the ETP phenotype in children with T-cell ALL, address knowledge gaps in the management of chronic granulomatous disease and learn about the effects of pathogenic and likely pathogenic variants for inherited hemostasis disorders.

On today's episode we’ll discuss the findings from a phase 2 study of sorafenib plus intensive chemotherapy in newly diagnosed FLT3-ITD AML, learn more about the inhibition of PLK4 in TP53-mutated AML, and discuss the role of CD44 in Plasmodium falciparum infection.

On today’s podcast we'll discuss high-risk cytogenetic abnormalities in solitary bone plasmacytomas. Then, we'll consider complement activation in vaso-occlusive pain episodes and how targeting C5a generation inhibited those effects. Finally we'll explore the genetics of platelet reactivity and how researchers used this data to develop a genetic score that was associated with risk of thrombotic diseases.

On this week's episode we’ll discuss the findings from a long-term follow up study of fludarabine, cyclophosphamide, and rituximab in IGHV-mutated CLL, learn more about the impact of genetic alterations and minimal residual disease in adults with KMT2A-rearranged B-cell precursor ALL, and discuss a pre-clinical study of reinforced immunotherapy for myeloma using a new bispecific antibody-based approach.

In this week's episode we'll discuss if fractionated dosing of gemtuzumab ozogamicin provide additional benefit over a single dose in older adults with AML. Then, we'll consider how the loss-of-function of ENT3 drives histiocytosis. Researchers describe a novel pathway leading to histiocytosis that involves hyperactivation of TLR-MAPKinase signaling. This suggests a potential benefit of MAPKinase -directed targeted therapy in a range of histocytoses. Finally we'll discuss unraveling resistance mechanisms to anti-CD20 treatments in B-cell malignancies. Through alternative splicing, the MS4A1 gene encoding human CD20 generates multiple mRNA isoforms with distinct 5’ untranslated regions. 

In this bonus episode of Blood Podcast, Coordinating Editor, Dr. Jason Gotlib is joined by Drs. Sioban Keel, Margaret Ragni, and Andoni Echaniz-Laguna to discuss the Review Series on RNA Therapeutics in Hematology. The series highlights areas in which RNA therapeutics are most advanced: acute hepatic porphyria, transthyretin amyloidosis, and hemophilia.

Review Series on RNA Therapeutics in Hematology

In this week's episode we’ll discuss the prognostic significance of splicing factor gene mutations in newly diagnosed AML, learn more about the findings from a multi-omics study of therapy resistance in multiple myeloma, and discuss the effects of KIT ligand deletion on systemic KIT levels and hematopoietic stem cell homeostasis. 

In this week's episode we'll see how targeting the prostacyclin receptor is a promising strategy for regulating hemostasis and thrombosis. Then, we'll learn how new evidence indicates that the progression rate is low in MRD-negative myeloma patients who discontinue post-transplant lenalidomide and dexamethasone maintenance therapy after 2 years. Finally we'll discuss how amphiregulin from leptin receptor-positive niche cells in the bone marrow mediates crosstalk between the niche and hematopoietic stem cells under conditions of DNA repair deficiency and aging.

In this week's episode, we discuss the findings from a phase 2 study of lenalinomide plus rituximab in elderly frail patients with DLBCL, learn more about platelet GP6-mediated neutrophil recruitment in early stages of acute lung injury, and discuss a newly identified isoform of the tyrosine kinase AXL, termed AXL3, in mantle cell lymphoma.

In this week's episode, we'll learn how the diversity of gut microbiota predicts mortality and acute graft-versus-host disease in pediatric allogeneic transplant recipients. Then we'll discuss complement inhibition in patients with complement-mediated atypical hemolytic uremic syndrome. Finally we'll learn how PD-1 plus HDAC equals responses in previously treated Hodgkin lymphoma, specifically that response rates were encouraging in a heavily pretreated cohort, even among patients with PD-1 refractory disease.  

In this week's episode, we’ll discuss a phase two trial in patients with T-cell large granular lymphocytic leukemia treated with the inhibitor BNZ-1 to block receptor binding of IL-15, learn more about the outcomes of gene therapy for Wiskott-Aldrich syndrome, and discuss ways to mitigate inequity when prioritizing patients for CAR T-cell therapy. 

In this week’s episode, we’ll learn that Germline pathogenic variants of the DDX41 gene are relatively common in the general population and linked to higher risk of AML and MDS, discuss the birtamimab plus standard of care in light chain amyloidosis, and review new insights on rare movement and neurocognitive toxicities that are observed after BCMA-directed CAR T cell treatment. 

In this weeks episode, we’ll learn more about the role of IL-7 receptor signaling in the differentiation and expansion of human B-cell progenitors, discuss the use of fixed-duration venetoclax plus obinutuzumab in older patients with chronic lymphocytic leukemia, and learn how low-density lipoprotein promotes microvascular thrombosis by enhancing von Willebrand Factor self-association 

In this week’s episode, we discuss real-world evidence for CAR T cell therapy in older patients with diffuse large B-cell lymphoma, inhibiting endogenous anticoagulant pathways in congenital factor deficiencies, and finally targeting the HSP90 epichaperome in acute myeloid leukemia. 

In this week's episode, we'll discuss the findings from the final analysis of the CLL2-GIVe trial, learn how NOTCH2 mutants promote resistance to chemotherapy in diffuse large B-cell lymphoma, and discuss the role of DBY/HLA class II complexes in chronic graft-versus-host disease.

In this week's episode, we’ll learn about long-term outcomes with pembrolizumab in relapsed/refractory classical Hodgkin lymphoma. Next, what’s behind the accumulation of toxic free alpha-globin in beta-thalassemia? Finally, a road map for managing CAR T cell hematologic toxicity. 

Blood associate editors Jeanne Hendrickson and Thomas Ortel edited a How I Treat series on inpatient consultative hematology. In this timely series of articles, the authors present an approach to bleeding, thrombosis, anemia, and quantitative neutrophil abnormalities.

In this week's episode, we’ll learn more about the treatment of relapsed and refractory cutaneous T-cell lymphoma with dimethyl fumarate, discuss the use of lipid nanoparticles for ex vivo editing of human hematopoietic cells, and learn more about racial and geographic disparities in lymphoma clinical trials.

In this week’s episode, we’ll review a detailed safety profile of acalabrutinib versus ibrutinib in patients with previously treated chronic lymphocytic leukemia, discuss a report that leukocyte inflammation contributes to trauma-induced coagulopathy by oxidation and degradation of fibrinogen, and finally, discuss a pharmacokinetic-pharmacodynamic analysis that shows higher abatacept exposure decreases occurrence of acute graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) from an unrelated donor. 

In this week’s episode, we’ll discuss pembrolizumab after autologous stem cell transplantation in patients with peripheral T-cell lymphoma. Newly reported phase 2 study results show that blocking PD-1 with pembrolizumab had a favorable safety profile and demonstrated promising activity, supporting further confirmatory studies in this setting; germline genetic predisposition to myeloid neoplasms in patients with hypoplastic bone marrow. Researchers report mutations that are significantly associated with cytopenias in adulthood in these patients. And pathogenic or likely pathogenic variants were linked to severe cytopenias and advanced myeloid malignancies; and finally, if monocytes and their descendants are less plastic than previously thought. Investigators have identified four functionally specialized monocyte subsets that derive from specific myeloid progenitor lineages. They show that the fate of these monocyte subsets is epigenetically scripted, with little flexibility after differentiation begins, even under conditions of stress.

In this week’s bonus episode of Blood Podcast, Associate Editor, Dr. John Crispino discusses the Review Series on Hematopoietic Stem Cells with authors, Dr. David Kent and Dr. Jennifer Trowbridge.   

Review Series on Hematopoietic Stem Cells

In this week's episode, we’ll learn more about what whole genome sequencing reveals about genetic subtypes of follicular lymphoma and risk of transformation, discuss the role of the lipid mediator, resolvin D4, in infectious neutrophil deployment and emergency granulopoiesis, and learn more about Hodgkin lymphoma-directed therapy and the role of PET in early-stage nodular lymphocyte-predominant Hodgkin lymphoma. 

In this week's episode, we'll learn more about ventricular arrhythmias in sickle cell anemia, discuss the molecular heterogeneity of pediatric monomorphic post–solid organ transplant lymphoproliferative disorders, and uncover the role of the bone marrow microenvironment as a driver of myeloid disorders.

In this week’s episode, we discuss the impact of silent cerebral infarction in patients with immune mediated thrombotic thrombocytopenic purpura (or iTTP) in clinical remission, how the survival of leukemia stem cells is highly dependent on oxidative phosphorylation in the mitochondria, and targeting iron import as a potential therapeutic approach in aggressive natural killer cell leukemia (or ANKL).

In this week's episode, we’ll learn more about poverty and relapse risk in children with ALL, discuss eligibility criteria and enrollment of diverse racial and ethnic populations in multiple myeloma clinical trials, and learn more about clonal hematopoiesis in VEXAS syndrome.

In this week's episode, we'll discuss if some patients with relapsed or refractory primary mediastinal B-cell lymphoma can be cured by checkpoint blockade alone. Next, autologous CAR T cells are highly effective, yet not always feasible in children with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Lastly, we'll discuss ironing out beta-thalassemia during pregnancy.

In this week's episode, we’ll discuss the findings from a study attempting gene therapy for WHIM syndrome for the first time, learn more about the fate of hematopoietic stem cells after transplantation, and discuss the role of C-terminal FGF23 peptides in iron conservation.

In this week's episode, we'll discuss new evidence on the critical role of hepcidin, the master regulator of iron metabolism, in the pathogenesis of polycythemia vera. Next, costimulatory molecules regulate mechanisms of CAR T cell dysfunction. Finally, we'll discuss how TREM2 is a novel receptor for IL-34, promoting differentiation of normal and leukemic myeloid cells. 

In this week’s episode we’ll report on the findings from a phase 2 trial of bone marrow transplantation as initial therapy for patients with severe aplastic anemia, discuss the utility of a PET radiomics-based model in predicting outcomes in diffuse large B-cell lymphoma, and learn more about macrophage metabolic rewiring in sickle cell disease.

In this week’s episode we will review no survival benefit for vincristine/steroid pulses in contemporary studies of childhood acute lymphoblastic leukemia (or ALL). Next, the rheumatology drug abatacept may be a promising strategy for the treatment of acute graft-versus-host disease (or GVHD). Finally, we'll discuss the hemorrhage risk of dasatinib therapy.

In this week’s episode, we'll discuss how patients with relapsed or refractory Hodgkin lymphoma survival outcomes have improved after development of several novel agents. Next, precision engineering of therapeutic T cells through extragenic safe harbors. Finally, using a single-cell atlas to map features of imatinib resistance in diagnostic CML bone marrow, investigators present gene expression signatures predictive of response to TKI therapy.

In this week’s episode we’ll discuss the findings from a study exploring the combination of concurrent pembrolizumab, adriamycin, vinblastine, and dacarbazine in newly diagnosed classical Hodgkin lymphoma, learn more about the effects of targeting the CD40/CD40-ligand axis in Waldenström Macroglobulinemia, and review the findings from a study aimed at improving the bone marrow homing of CAR-cytokine induced killer cells in AML.

In this bonus episode, Associate Editor, Dr. Helen Heslop discusses the How I Treat series on Emergent CAR-T cell toxicities with authors Dr. Fabiana Perna, Dr. Natalie Grover and Dr. Nirali Shah.

In this week’s episode, we will review patients with chronic ITP having clonal expansions of a specific subset of CD8 T cells, called terminally differentiated effector memory T cells, or TEMRA. Next, for patients with diffuse large B-cell lymphomas, use of a so-called dark-zone signature, previously referred to as the double-hit signature, could help refine prognosis. Finally on today's podcast we'll discuss rethinking the role of hematopoietic stem cells following physiologic emergencies such as acute inflammation and blood loss.

In this special episode, Trainee Council Chairs, Drs. Becky Zon and Ajay Major, interview Dr. Nancy Berliner, Blood Editor-in Chief and Dr. Andrew Roberts, Blood Deputy Editor, on their careers in academic editing and publishing, including career development tips for trainees who are interested in a career in publishing.

In this week’s episode we’ll report on the findings from a 5-year follow-up study of axicabtagene ciloleucel in refractory large B-cell lymphoma, discuss the role of C1 inhibitor deficiency in coagulation and venous thrombosis, and learn how chemotherapy signatures can be used to track the evolution of therapy-related myeloid neoplasms.

In this week’s episode we'll review imbalances in gut microbiota may impact the efficacy and safety of immunochemotherapy in patients with diffuse large B-cell lymphoma. Next, the NFIA-ETO2 fusion, found exclusively in pediatric patients with pure erythroid leukemia, impairs the normal process of erythroid differentiation. Finally, we'll look at the effectiveness of nirmatrelvir plus ritonavir in patients with CLL infected with SARS-CoV-2 during the Omicron surge.  

In this week’s episode, we’ll discuss the newly revised International Working Group response criteria for patients with higher-risk MDS, learn more about the utility of machine learning in the differential diagnosis of bone marrow failure, and discuss whether patients with the Asian-type DEL allele, who type as serologic Rh-D-negative, can be safely transfused with RhD-positive blood.

In this week’s episode we will review treatment and outcomes for patients with autoimmune hemolytic anemia during pregnancy. Next, rapid immune tolerance induction in patients with hemophilia A and high-titer inhibitors. Finally, researchers compare kinetics and cell cycle progression in hematopoietic stem cells from cord blood, young adults, and aged healthy donors.

In this episode Associate Editor, Dr. Mario Cazzola discusses the review series on Classical Myeloproliferative Neoplasms, with authors, Dr. Ann Mullaly and Dr. Alison Moliterno. 

Review Series on Classical Myeloproliferative Neoplasms

In this week’s episode, we’ll learn how rare germline genetic variants in complement factor H (CFH) affect the course of paroxysmal nocturnal hemoglobinuria, discuss the role of coagulation factor XII in thrombotic complications and vaso-occlusion associated with sickle cell disease, and learn more about the overlapping features of therapy-related and de novo NPM1-mutated AML.

In this week’s episode we will review optimizing the value of post-transplant lenalidomide maintenance in multiple myeloma. Next, T-cell immunotherapies targeting AML antigens upregulate MHC Class II expression on AML cells. Finally, young bugs rejuvenate old blood: transplanting fecal microbiota from younger mice into older mice improved hematopoietic stem cell function and restored lymphoid differentiation potential.

In this bonus episode Associate Editor, Dr. Mario Cazzola discusses the review series on Germline predisposition to hematologic malignancies with authors, Dr. Lucy Godley, Dr. Anna Brown, and Dr. Dennis Hickstein.   

Review Series on Germ Line Predisposition to Hematologic Malignancy

In this week’s episode we’ll learn how HLA-E-restricted immune responses help control Epstein-Barr virus infection, discuss the activity of NRX-0492 in chronic lymphoblastic leukemia, and learn more about the efficacy of non-steroid inflammatory drugs in the treatment of bone marrow failure associated with Ghosal Hematodiaphyseal Dysplasia.

In this week’s episode we will review a study in sub-Saharan Africa where treatment of sickle cell anemia with hydroxyurea is associated with a lower incidence of malaria. New research suggests mild myelosuppression associated with hydroxyurea treatment may actually have a salutary effect. Next, a potential new treatment approach in lower GI acute GVHD. Adding an interleukin-22 therapy to corticosteroid treatment was well tolerated with a high rate of response in this very challenging patient population. Finally, common AML driver mutations such as FLT3ITD (or internal tandem duplications) orchestrate distinct transcriptional and epigenetic programs based on different genetic contexts. In the context of a common pediatric AML mutation, FLT3ITD selectively activated type I interferon signaling, suggesting a distinct therapeutic vulnerability.

In this week’s episode we’ll discuss how azacytidine therapy influences the contributions of mutated HSC clones to hematopoiesis in MDS and CMML, learn more about the risk of venous thromboembolism in patients with adult-type diffuse glioma, and discuss the importance of 1p32 deletions as an independent and adverse prognostic factor in myeloma.

In this week’s episode we will review an imbalance among RUNX1 isoforms is key to the pathogenesis of trisomy 21-associated myeloid leukemia, raising the possibility that equilibrium could be restored genetically or pharmacologically. Next, an RNA aptamer demonstrating promising results in patients with hemophilia A. Lastly, phase 2 data on valemetostat, a selective inhibitor of EZH1 and 2, in relapsed or refractory adult T-cell leukemia/lymphoma.

In this week’s episode, we’ll discuss the findings from a phase 3 trial of PI3Kδ inhibitor leniolisib in activated PI3Kd syndrome, learn more about the efficacy and safety of dabrafenib plus trametinib in relapsed/refractory BRAF V600E mutation-positive hairy cell leukemia, and review the findings from a study conducted in an international cohort of patients with Tγδ LGL leukemia.

In this bonus episode Associate Editor, Dr. Helen Heslop discusses Banked Allogeneic Immune Effector Cells with Blood author Dr. Jeffrey Miller. 

Review Series on Banked Allogeneic Immune Effector Cells

In this week’s episode we will first review a new clinical trial evidence that for patients with sickle cell anemia in resource limited settings, both low and moderate dose hydroxyurea are effective for secondary stroke prevention. Next, a research article showing how secreted mutant calreticulin functions as a “rogue cytokine” in myeloproliferative neoplasms, acting in a paracrine manner to promote growth of nearby tumor cells. Finally, we’ll review new research on the pathobiology of adult and pediatric Burkitt lymphoma. With the help of whole-genome sequencing, investigators unraveled distinct subgroups, which may provide a new framework for epidemiology, diagnosis, and treatment of these lymphomas.

In this week’s episode we’ll discuss the benefits of early diagnosis and hematopoietic stem cell transplant in patients with hypomorphic RAG deficiency, learn more about EBV-driven lymphoid neoplasms associated with pediatric ALL maintenance therapy, and analyze the associations between clonal hematopoiesis and recurrent vascular events and death in patients with ischemic stroke. 

In this week's episode, we’ll discuss the dynamics of measurable residual disease, or MRD, over time in myeloma patients undergoing ixazomib maintenance. Serial measurements were feasible and provided more detailed risk stratification than single timepoint measurements—findings that could have implications for the use of MRD to guide treatment duration. Up next, a research article exploring the relationships between poverty, and lack of neighborhood opportunity, with outcomes of CAR T -cell therapy in children with acute lymphoblastic leukemia. The findings suggest opportunities for interventions to improve access for less socioeconomically advantaged children. Finally, we’ll review a report demonstrating that acquired mutations in the pro-apoptotic effector protein BAX are common in patients with AML treated with venetoclax. These and other research observations reveal BAX variants as a hurdle to the long-term success of BCL2-targeted therapy in this disease.

In this bonus episode Associate Editor, Dr. Bertie Göttgens and Dr. Ravi Majeti discuss the series on Single Cell Genomics and Heme Malignancies-Leukemia/MPNs.   

Blood Review Series on Single-Cell Genomics

Megakaryocytes contribute to multiple processes in the body, including platelet production and regulation of hematopoietic stem cells. Therefore, it is not surprising that alterations in this lineage not only affect platelets but also impact hematopoiesis in other ways. Fortunately, our understanding of megakaryocyte biology has increased significantly with the advent of advanced technologies such as next-generation sequencing and sophisticated microscopy.

Blood Review Series on Megakaryopoiesis and Platelet Production

To reach the goal of curing currently incurable hematologic malignancies, we need to go beyond focusing on single gene mutations and gain deeper understanding of the consequences of genetic alterations on gene-regulatory pathways. Edited by John Crispino, these 5 cutting-edge reviews from leaders in the their fields not only summarize our current understanding of key pathways that contribute to myeloid malignancies, but also discuss new therapeutic avenues related to them. They provide a springboard for further groundbreaking basic and clinical advances in hematologic malignancies.

Review Series on Mechanisms of Hematologic Malignancies

Platelets are critical for hemostasis and thrombosis, but recent research highlights their role in many other processes, including inflammation, wound healing, and lymphangiogenesis. In this episode, Drs. José López, Elisabeth Battinelli, Craig Williams, and Owen McCarty discuss the review series on platelets and cancer. The series focuses on the emerging role of platelets in cancer, influencing tumor growth and metastasis, immune evasion, and tumor angiogenesis. The reviews present the current understanding of mutual cross talk between platelets and tumors, communication mediated by RNA transfer and extracellular vesicles, and the potential of antiplatelet agents for cancer treatment.

Review Series on Platelets and Cancer

In this bonus episode, we welcome Blood Associate Editor, Dr. Margaret Goodell, along with colleagues Dr. Grant Challen and Dr. David Steensma as they discuss the Blood review series on  mechanisms and clinical implications of clonal hematopoiesis. The articles in this series review the mechanisms driving the development of clonal hematopoiesis, the associated risks posed by clonal hematopoiesis for patients with hematologic and nonhematologic disorders and patients with inherited bone marrow syndromes, and the clinical ramifications of discovering clonal hematopoiesis and sharing the results with patients.

Review Series on Mechanisms and Clinical Implications of Clonal Hematopoiesis

In this bonus episode, we welcome Drs. Mario Cazzola, Rachel Grace, and Achille Iolascon as they discuss the Blood Review Series on Inherited Anemias. In this series, experts review the biology and pathophysiology of prominent inherited anemias and provide updated information on their management.

Review Series on Inherited Anemias

In this bonus podcast episode Dr. Jean Soulier shares highlights of the Blood Review Series on Secondary Leukemia. In this review series, experts provide new insights into the pathobiology of secondary acute myeloid leukemias arising in diverse genetic or acquired, benign or malignant hematologic disorders.

Review Series on Secondary Leukemia

In this bonus podcast episode, Drs. Nancy Berliner and Laurie Sehn lead a discussion on this series of authoritative reviews on a collection of rare systemic hematologic disorders that are frequently difficult to recognize, diagnose, and treat. The series highlights new genomic and proteomic insights that inform our understanding of their pathophysiology and treatment.

Review Series on Rare Systemic Hematologic Disorders

In this episode Dr. Catherine Bollard, Blood Associate Editor provides highlights of this commissioned review series Understanding and Treating Primary Immunodeficiency, that highlights cutting-edge developments in the biology and management of primary immune deficiencies.

Review Series on Understanding and Treating Primary Immunodeficiency

This week’s episode will review treatment for secondary prevention of venous thromboembolism in children, a therapeutic strategy for relapsed or refractory B-cell acute lymphoblastic leukemia, Ivosidenib monotherapy in patients with newly diagnosed AML with mutations in the isocitrate dehydrogenase 1 gene, and survival outcomes of chronic Lymphocytic Leukemia patients treated with Ibrutinib.

This week’s episode will examine the critical role of platelet necrosis in ischemic stroke injury, the discovery of the molecular basis for the PEL blood group, and the impact of NPM1/FLT3-ITD genotypes in patients with acute myeloid leukemia.

In this episode we welcome Drs. Thomas Ortel, Jeffrey Weitz, and Kenneth Bauer as they discuss the Blood Review Series on the Treatment of Venous Thrombotic Disorders. In this review series, experts contribute 6 seminal reviews that focus on the treatment of venous thromboembolism (VTE) in adults and children, the management of VTE developing in unusual locations and in the setting of thrombophilia, and new targets and antithrombotic therapies in development.

Review Series on Treatment of Venous Thrombotic Disorders

In this episode we’ll examine a new strategy to improve the durability of remission after CAR T-cell therapy for pediatric B cell leukemia, explore the genomic landscape of Breast Implant-Associated Anaplastic Large Cell Lymphomas, and discuss a new report showing that the occurrence of arterial thrombotic events following the diagnosis of myeloproliferative neoplasms is associated with a significantly increased risk of a second cancer.

The article highlighted in this trailer "The chromatin-binding protein Phf6 restricts the self-renewal of hematopoietic stem cells"  was published June 6, 2019; Blood, Volume 133, Issue 23. 

The authors of this article are: Satoru Miyagi , Patrycja Sroczynska , Yuko Kato , Yaeko Nakajima-Takagi , Motohiko Oshima , Ola Rizq , Naoya Takayama , Atsunori Saraya , Seiya Mizuno , Fumihiro Sugiyama , Satoru Takahashi , Yumi Matsuzaki , Jesper Christensen , Kristian Helin , Atsushi Iwama.