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
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).
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
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
My Cancer Genome has released its new and improved cancer clinical trials search tool on our
beta website. Please visit beta.padiracinnovation.org
to check it out!