Normal Function
The FLT3 gene provides instructions for making a protein called fms-like tyrosine kinase 3 (FLT3), which is part of a family of proteins called receptor tyrosine kinases (RTKs). 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 cell types where a specific protein called FLT3 ligand, or FL, can attach (bind) to it. This binding turns on (activates) the FLT3 protein, which subsequently activates a series of proteins inside the cell that are part of multiple signaling pathways. The signaling pathways stimulated by the FLT3 protein control many important cellular processes such as the growth and division (proliferation) and survival of cells, particularly of early blood cells called hematopoietic progenitor cells.
Health Conditions Related to Genetic Changes
Core binding factor acute myeloid leukemia
MedlinePlus Genetics provides information about Core binding factor acute myeloid leukemia
More About This Health ConditionCytogenetically normal acute myeloid leukemia
Changes in the FLT3 gene are involved in a form of blood cancer known as cytogenetically normal acute myeloid leukemia (CN-AML). While large chromosomal abnormalities can be involved in the development of acute myeloid leukemia, about half of cases do not have these abnormalities; these are classified as CN-AML.
The FLT3 gene mutations involved in CN-AML are called somatic mutations; they are found only in cells that become cancerous and are not inherited. Two types of FLT3 gene mutations are found in CN-AML. The most common, which occurs in up to 34 percent of CN-AML cases, is called the FLT3 internal tandem duplication (FLT3-ITD). In this type of mutation, a short sequence of DNA is copied and inserted directly following the original sequence. The duplicated DNA sequence can vary in size, but all FLT3-ITD mutations result in alterations in the region of the protein that spans the cell membrane, known as the juxtamembrane domain. The altered juxtamembrane domain allows the FLT3 receptor to activate signaling pathways without binding of FL; the receptor is always turned on and is said to be constitutively activated. Constant signaling leads to uncontrolled proliferation of abnormal, immature white blood cells, a hallmark of acute myeloid leukemia.
The other type of FLT3 gene mutation is found in about 14 percent of people with CN-AML. These mutations are referred to as FLT3-TKD mutations because they change single protein building blocks (amino acids) in a region of the protein known as the tyrosine kinase domain (TKD). The most commonly changed amino acid is asparagine at position 835; it is typically replaced by the amino acid tyrosine. This mutation is written as Asp835Tyr or D835Y. Like FLT3-ITD mutations, FLT3-TKD mutations result in a constitutively activated FLT3 receptor and constant signaling, leading to acute myeloid leukemia.
More About This Health ConditionOther Names for This Gene
- CD135
- CD135 antigen
- fetal liver kinase 2
- FL cytokine receptor
- FLK-2
- FLK2
- FLT3_HUMAN
- fms-like tyrosine kinase 3
- fms-related tyrosine kinase 3
- growth factor receptor tyrosine kinase type III
- receptor-type tyrosine-protein kinase FLT3
- stem cell tyrosine kinase 1
- STK-1
- STK1
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Choudhary C, Schwable J, Brandts C, Tickenbrock L, Sargin B, Kindler T, Fischer T, Berdel WE, Muller-Tidow C, Serve H. AML-associated Flt3 kinase domain mutations show signal transduction differences compared with Flt3 ITD mutations. Blood. 2005 Jul 1;106(1):265-73. doi: 10.1182/blood-2004-07-2942. Epub 2005 Mar 15. Citation on PubMed
- Gilliland DG, Griffin JD. The roles of FLT3 in hematopoiesis and leukemia. Blood. 2002 Sep 1;100(5):1532-42. doi: 10.1182/blood-2002-02-0492. Citation on PubMed
- Kiyoi H, Ohno R, Ueda R, Saito H, Naoe T. Mechanism of constitutive activation of FLT3 with internal tandem duplication in the juxtamembrane domain. Oncogene. 2002 Apr 11;21(16):2555-63. doi: 10.1038/sj.onc.1205332. Citation on PubMed
- Li L, Piloto O, Kim KT, Ye Z, Nguyen HB, Yu X, Levis M, Cheng L, Small D. FLT3/ITD expression increases expansion, survival and entry into cell cycle of human haematopoietic stem/progenitor cells. Br J Haematol. 2007 Apr;137(1):64-75. doi: 10.1111/j.1365-2141.2007.06525.x. Citation on PubMed
- Yamamoto Y, Kiyoi H, Nakano Y, Suzuki R, Kodera Y, Miyawaki S, Asou N, Kuriyama K, Yagasaki F, Shimazaki C, Akiyama H, Saito K, Nishimura M, Motoji T, Shinagawa K, Takeshita A, Saito H, Ueda R, Ohno R, Naoe T. Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. Blood. 2001 Apr 15;97(8):2434-9. doi: 10.1182/blood.v97.8.2434. Citation on PubMed
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