Research findings could help inform more effective therapies for AML
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.
