Blasts with erythroid or megakaryocytic differentiation (AEL and AMKL, respectively) express high levels of BCL-xL and are uniquely vulnerable to BCL-xL inhibition. In contrast, BCL-2 and MCL1 expression are generaly increased in acute myeloid (AML) and monocytic (AMoL) leukemia, respectively. AEL and AMKL also demonstrate sensitivity to the JAK inhibitor, ruxolitinib, and the combined inhibition of BCL-xL and JAK leads to enhanced cell death. Figure created with BioRender.com.