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URL of this page: https://medlineplus.gov/genetics/gene/flt3/

FLT3 gene

fms related receptor tyrosine kinase 3

Normal Function

The FLT3 gene provides instructions for making a protein that is part of a family of proteins called receptor tyrosine kinases. Receptor tyrosine kinases transmit signals from the cell surface into the cell through a process called signal transduction. The FLT3 protein is found in the outer membrane of certain cells, including blood-forming cells, where it can bind to a specific protein called FLT3 ligand (FL).

When the FLT3 protein binds to FL, the FLT3 protein turns on. This activates a series of proteins inside the cell that are part of multiple signaling pathways. The signaling pathways that are activated by the FLT3 protein control many important cellular processes, such as cell growth and division (proliferation) and cell survival, particularly in blood-forming cells.

Health Conditions Related to Genetic Changes

Cytogenetically normal acute myeloid leukemia

Genetic changes that contribute to disease are called pathogenic variants. Pathogenic variants in the FLT3 gene are frequently found in people with a form of cancer known as cytogenetically normal acute myeloid leukemia (CN-AML). CN-AML is a type of acute myeloid leukemia (AML), which is a cancer of the blood and blood-forming tissue (bone marrow). People with CN-AML do not appear to have the large chromosomal abnormalities that are sometimes involved in the development of AML.

The pathogenic variants in the FLT3 gene that are associated with CN-AML are acquired during a person's lifetime (somatic) and are found only in cancer cells. Cells that contain FLT3 pathogenic variants typically have increased proliferation.

Two types of FLT3 somatic variants are commonly found in people with CN-AML. The most common variant is the FLT3 internal tandem duplication (FLT3-ITD), which is found in approximately 25 percent of people with CN-AML. With this type of variant, a short sequence of DNA is duplicated and inserted directly after the original sequence. The duplicated DNA sequence can vary in size, with insertions ranging between three DNA building blocks (base pairs) to over 300 base pairs. The FLT3-ITD variants alter a region of the protein known as the juxtamembrane domain. This change allows the FLT3 receptor to activate signaling pathways without binding to FL. As a result, the receptor is always turned on, leading to the overactivation of multiple signaling pathways. The activation of these signaling pathways contributes to the uncontrolled proliferation of abnormal, immature white blood cells that is seen in people with CN-AML. Some people with CN-AML have multiple FLT3-ITDs, and people with CN-AML who have pathogenic variants in the FLT3 gene often have variants in additional genes as well. Detecting FLT3-ITD variants is important for the diagnosis and treatment of CN-AML.

Another common FLT3 gene variant that is associated with CN-AML is called an FLT3-TKD variant because it affects a region of the protein called the tyrosine kinase domain (TKD). The FLT3-TKD variant is found in approximately 7 percent of people with CN-AML. The most common FLT3-TDK pathogenic variant replaces the protein building block (amino acid) aspartic acid at position 835 with a different amino acid. Like FLT3-ITD variants, FLT3-TKD variants also result in the overactivation of multiple signaling pathways, which can lead to the proliferation of abnormal white blood cells and the development of CN-AML.

More About This Health Condition

Acute promyelocytic leukemia

MedlinePlus Genetics provides information about Acute promyelocytic leukemia

More About This Health Condition

Core binding factor acute myeloid leukemia

MedlinePlus Genetics provides information about Core binding factor acute myeloid leukemia

More About This Health Condition

Other disorders

Somatic variants in the FLT3 gene have also been found in people with some forms of AML that do involve large chromosomal abnormalities (cytogenetically abnormal AML). In these cases, people may have somatic FLT3 variants in addition to various chromosomal abnromalities. Acute promyelocytic leukemia (APL) is an example of a form of AML that is caused by the combination of somatic FLT3 variants and various chromosomal abnormalities.

Somatic variants in the FLT3 gene have been found in people with other blood cell cancers, including in approximately 5 percent of people with acute lymphoblastic leukemia (ALL). ALL is a fast-growing cancer that involves white blood cells called lymphocytes.

Other Names for This Gene

  • CD135
  • FLK2
  • STK1

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Gene and Variant Databases

References

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