New Brunswick, N.J., April 24, 2023—Acute myeloid leukemia (AML) is a type of cancer in which the bone marrow makes a large number of abnormal blood cells. It is the most common type of acute leukemia in adults.
Background:
For decades, the treatment options for this disease have included chemotherapy and bone marrow transplant, however, newer therapeutics termed ‘BH3-mimetic drugs’, are recently introduced or being explored to treat patients with AML. BH3-mimetics have been developed to directly activate apoptosis (a form of programmed cell death) in malignant cells, thus selectively killing leukemia cells. Not all AML patients respond to BH3-mimetic treatments, with some developing treatment resistance. Investigators further examined the mechanism behind this new class of drugs.
Findings:
- Investigators examined the cancer cells which escape various BH3-mimetics treatments and found that these cells have higher levels of mitochondrial autophagy. With autophagy (deriving from the Greek words “auto” = “self” and “phagy” = “eating”), cells can “eat up” and recycle various damaged cellular components, like proteins or whole organelles (mitochondria). The specific process of self-eating injured mitochondria is called mitophagy.
- By quickly “eating up” their affected mitochondria, cancer cells limit damages caused by the BH3-mimetics drugs and maintain a healthy mitochondrial population. For this reason, the cancer cells eventually survive. This is the mechanism that cancer cells escape BH3-mimetics treatment and apoptosis.
- Novel compounds that block mitophagy can enhance the efficacy of BH3-mimetics in various AML models and can reverse drug resistance.
Implications: These findings will help inform more effective therapies for AML and propose novel combination treatments, say the study authors. The full study including author disclosures, funding and other can be found in Cancer Discovery: https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-22-0601
Christina Glytsou, PhD, co-author of the study, is a researcher and member of the Cancer Metabolism and Immunology Cancer Pharmacology Program at Rutgers Cancer Institute of New Jersey, the state’s leading cancer program and only National Cancer Institute-designated Comprehensive Cancer Center together with RWJBarnabas Health, and an assistant professor in the departments of Pediatrics at Rutgers Robert Wood Johnson Medical School and Chemical Biology at Rutgers Ernest Mario School of Pharmacy. She is available to discuss findings from this work, which was conducted at her previous institution, NYU Langone Health and NYU Grossman School of Medicine.
