Research findings could help inform more effective therapies for LAM

Acute myeloid leukemia (AML) is a type of cancer in which the bone marrow makes large numbers of abnormal blood cells. It is the most common type of acute leukemia in adults.

Background:

For decades, treatment options for this disease have included chemotherapy and bone marrow transplantation, however, new therapies called “BH3 mimetics” have recently been introduced or explored to treat patients with LAM. BH3 mimetics have been developed to directly activate apoptosis (a form of programmed cell death) in malignant cells, thereby selectively killing leukemic cells. Not all AML patients respond to BH3 mimetic treatments, with some developing resistance to treatment. Investigators have further examined the mechanism behind this new class of drugs.

Results:

• The researchers examined cancer cells that escape various BH3-mimetic treatments and found that these cells had higher levels of mitochondrial autophagy. With autophagy (derived from the Greek words “auto” = “self” and “phagy” = “eat”), cells can “eat” and recycle various damaged cellular components, such as proteins or whole organelles (mitochondria). The specific self-feeding process of injured mitochondria is called mitophagy.
• By quickly “eating” their affected mitochondria, cancer cells limit the damage caused by BH3-mimetic drugs and maintain a healthy mitochondrial population. Because of this, cancer cells eventually survive. This is the mechanism by which cancer cells escape treatment and apoptosis from BH3 mimetics.
• New compounds that block mitophagy may improve the effectiveness of BH3-mimetics in various AML models and can reverse drug resistance.

Consequences :

According to the study authors, these findings will help inform more effective therapies for AML and provide new combination treatments.