New Research Shows How Mutant IDH2 Fuels AML

In the past, researchers have shown that acute myeloid leukemia (AML) may be driven by certain genetic mutations. For example, some mutations might cause the abnormal or excess production of mutant proteins, such as IDH1 and IDH2. While these proteins normally play a part in energy production and cell metabolism, the mutant forms may spur cancer progression. Recently, researchers sought to understand how AML progresses and what impact mutant IDH2 has. According to Medical XPress, the researchers discovered the underlying mechanism of AML progression, which may help improve treatment in the future. Interested in learning more? Check out the study findings in Molecular Cell.

Mutant IDH2

Within this study, a research team from the University of Chicago Medicine Comprehensive Cancer Center explored how mutant IDH2 plays a role in AML progression. Unlike normal IDH protein, mutant proteins create 2-HG, a molecule which stops white blood cells from maturing. As a result, 2-HG plays a role in leukemia formation through the production of immature white blood cells. Findings from the study include:

  • AML cells have the ability to alter and regulate mutant IDH2. Through this, AML cells are able to produce a certain amount of 2-HG without producing it in excess.
    • This is important. Even though 2-HG may spur cancer progression, it can also be overly toxic for cancer cells. In moderate amounts, 2-HG causes cancer to progress; in excess, it causes cellular death. Thus, AML cells’ ability to modulate 2-HG production means that the cancer can drive its own progression while also protecting itself from destruction.
  • A protein called fms-like tyrosine kinase 3 (FLT3) modifies proteins and can either activate or inactive these proteins. This particular cancer uses FLT3 to regulate IDH2 levels.
  • The process of modifying mutant IDH2 is called acetylation. Through acetylation, AML cells lower 2-HG levels.

Through these findings, researchers now hold a better understanding of the mechanisms driving AML progression. Additionally, these findings are helpful in honing and developing better treatment options. Currently, the standard of care for this form of cancer includes chemotherapy, radiation, or certain medicines. Even though treatment options exist for mutant IDH1 and IDH2, researchers may now create more targeted solutions to address 2-HG production.

Acute Myeloid Leukemia (AML)

Acute myeloid leukemia, or acute myelogenous leukemia (AML), is a blood and bone marrow cancer. Normally, the bone marrow plays a role in blood cell production: white and red blood cells, as well as platelets. But in patients with AML, cell DNA damage causes the production of abnormal blood cells. Eventually, immature cells develop into myeloblasts, or leukemic cells. As these cells proliferate, they crowd out healthy cells, causing health issues. Risk factors include radiation exposure, being male, older age, and smoking cigarettes. Typically, AML also progresses fairly quickly. Symptoms include:

  • Lethargy and/or general malaise
  • Frequent infections
  • Shortness of breath
  • Fatigue
  • Fever
  • Bone pain
  • Easy bruising and bleeding
    • Note: This also includes abnormal and unusual bleeding, such as frequent or recurrent nosebleeds, or gum bleeding.
  • Pallor (pale skin)
Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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