New discoveries reveal how acute myeloid leukemia walks a fine line between growth and cell death

immature white blood cells in blood smear leukemia concept

Researchers revealed new insights into how acute myeloid leukemia (AML) develops and progresses, according to a study published in Molecular Cell on July 20, 2021. They describe a mechanism by which AML cells regulate a cancer-related protein, mutant IDH2, to increase the buildup of blood cancer cells—a distinguishing characteristic of the disease. This improved understanding of IDH2-related mechanism in AML will allow physicians to better understand how current IDH2-targeting medications work to ultimately improve treatments for AML patients.

AML is a cancer of the blood cells that can occur when immature white blood cells, cells that normally fight infection, acquire certain genetic mutations that cause them to multiply rapidly and build up the bone marrow and blood. It is the most common acute leukemia in adults and usually gets worse quickly if it is not treated.

This cancer can be driven by genetic mutations leading to the production of cancer-related mutant proteins, such as mutant IDH2 and IDH1. Normal IDH proteins are important in cell metabolism and play a role in the production of energy from the breakdown of molecules from food. The mutant forms of IDH proteins, found in AML cells, take on an extra function of making a cancer-causing molecule called 2-HG. 2-HG blocks the maturation of white blood cells, driving the development of leukemia.

Although 2-HG can drive the development of cancer, at high concentrations it becomes toxic, killing cancer cells. Researchers at the University of Chicago Medicine Comprehensive Cancer Center and their collaborators were interested in learning how mutant IDH2 drives the development of AML, and how the leukemia cells are able to regulate the production of 2-HG to promote spread and avoid cell death.

The research team, led by