Mitophagy Promotes Resistance to BH3 Mimetics in Acute Myeloid Leukemia.

Unlabelled: BH3 mimetics are used as an efficient strategy to induce cell death in several blood malignancies, including acute myeloid leukemia (AML). Venetoclax, a potent BCL-2 antagonist, is used clinically in combination with hypomethylating agents for the treatment of AML. Moreover, MCL1 or dual BCL-2/BCL-xL antagonists are under investigation.

STAT3 protects HSCs from intrinsic interferon signaling and loss of long-term blood-forming activity.

STAT3 function in hematopoietic stem and progenitor cells (HSPCs) has been difficult to discern as deficiency in the hematopoietic system induces systemic inflammation, which can impact HSPC activity. To address this, we established mixed bone marrow (BM) chimeric mice with CreER-mediated deletion in 20% of the hematopoietic compartment. -deficient HSPCs had impaired hematopoietic activity and failed to undergo expansion in BM in contrast to -sufficient (CreER) controls.