In this week’s episode, we review results of preclinical investigations that sound a note of caution regarding the potential use of JAK inhibitors as treatment for hemophagocytic lymphohistiocytosis (or HLH), research that provides new insights on how CD44 loss of function sensitizes AML cells to the BCL-2 inhibitor venetoclax, and conclude with a report that demonstrates cooperation between B cell receptor signaling and genetic lesions in CDKN2A, CDKN2B and TP53 in Richter transformation.