Acute Myeloid Leukemia: FLT3-ITD Mutation

What is Acute Myeloid Leukemia (AML)?

  • Acute: Describes the rapid progression of the disease and the immediate need for treatment.
  • Myeloid: Refers to the Myeloid blood cell line, which is responsible for the formation of red blood cells, platelets, and some types of white blood cells.
  • Leukemia: Type of cancer that originates in cells that normally develop into different types of blood cells.

AML begins in the bone marrow and can move into the blood to travel throughout the body. The errors in the maturation of the myeloid line of blood cells causes the growth and accumulation of abnormal white blood cells that interfere with normal blood cell production (Pollyea et al. 2011).

Why is this disease of interest?

Acute myeloid leukemia (AML) is the most common type of acute leukemia among adults and causes the largest number of deaths from leukemias annually in the United States (Döhner et al. 2015). Majority of AML patients are elderly and have survival rates comparable to patients with metastatic renal or lung cancer, with a 5- year overall survival range of 5-15% (Sekeres 2008).

What’s hot in the literature?

Mutations are common in AML and are extremely important for cancer diagnosis as well as survival. For example, mutations in FLT3, a receptor involved in stimulating cell growth,  represents one of the most frequent, but clinically challenging types of AML mutations (Zheng et al. 2003). Patients with a particular type of  FLT3 mutation, the FLT3-ITD mutation, generally experience an increased relapse risk, meaning a greater chance of the cancer returning after treatment, and consequently, a shorter overall survival time (Pollyea et al. 2011).

Patients with a FLT3-ITD mutation often cannot be cured with standard chemotherapy treatment. This has led to the development of highly specific targeted therapies for mutated FLT3-ITD AML cells. Since the discovery of the FLT3-ITD mutation, approximately 20 different FLT3 inhibitors have been developed, shedding some hope for a potential cure in the future (Levis 2013).

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