• What is FLT3?
  • FLT3 in Acute Myeloid Leukemia
  • Clinical Trials

FLT3

Fms-related tyrosine kinase 3 (FLT3) is a gene that encodes for a tyrosine kinase that activates pathways in hematopoietic cells (Gene 2013) important in cellular proliferation. The FLT3 protein has an extracellular domain consisting of five immunoglobulin-like domains, a transmembrane domain, a juxtamembrane domain, and two tyrosine kinase domains (Leung, Man, and Kwong 2013).

FLT3 is frequently mutated in acute myeloid leukemia, myelodysplastic syndromes, other hematologic malignancies, and colorectal cancer (COSMIC​). Mutations in MDS are skewed towards the highest risk disease (refractory anemia with excess blasts).

Related Pathways

Contributors: Scott Wheeler, Ph.D. (through June 2014), Adam Seegmiller, M.D., Ph.D., Cindy L. Vnencak-Jones, Ph.D., Stephen A. Strickland, M.D., MSCI, Annette S. Kim, M.D., Ph.D.

Suggested Citation: Wheeler, S., A. Seegmiller, C. Vnencak-Jones, S. Strickland, A. Kim. 2016. FLT3. My Cancer Genome https://www.padiracinnovation.org/content/disease/acute-myeloid-leukemia/flt3/?tab=0 (Updated June 17).

Last Updated: June 17, 2016

FLT3 in Acute Myeloid Leukemia

FLT3 mutations are observed in 24.3% of AML (COSMIC). Of these, most are internal tandem duplications. FLT3 internal tandem duplication (ITD) occurs when sequences of less than ten to several hundred bases in length are repeated within the juxtamembrane domain (Fathi and Chen 2011; Kottaridis et al. 2001). All duplications are “in frame,” with the number of nucleotides added as a multiple of three. Corresponding new amino acids are inserted into the protein, but the coding frame of the protein remains unchanged. In addition to internal tandem duplications, point mutations have also been observed in the tyrosine kinase domain (TKD) of the FLT3 protein in 5-7% of AML patients. FLT3 ITD and FLT3 TKD mutations lead to aberrant activation of FLT3 signaling, leading to proliferation of tumor cells (Leung, Man, and Kwong 2013). FLT3 mutations fall into class I of the “two-hit” theory of leukemogenesis (Naoe and Kiyoi 2013).​

Contributors: Scott Wheeler, Ph.D. (through June 2014), Adam Seegmiller, M.D., Ph.D., Cindy L. Vnencak-Jones, Ph.D.

Suggested Citation: Wheeler, S., A. Seegmiller, C. Vnencak-Jones. 2013. FLT3 in Acute Myeloid Leukemia. My Cancer Genome https://www.padiracinnovation.org/content/disease/acute-myeloid-leukemia/flt3/ (Updated September 9).

Last Updated: September 9, 2013

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