FLT3

Functions

FMS-like receptor tyrosine kinase 3 (FLT3) plays an important role in the formation of early stem/progenitor cells during hematopoietic development.

Pathology

 mutations in the FLT3 gene

• in acute myeloid leukaemia (AML) (25%-30% of cases) (most common genetic lesion)
• mutations in the FLT3 gene in childhood hyperdiploid acute lymphoblastic leukemia

 reduce survival in acute myeloid leukaemia (AML)

FMS-like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes in acute myeloid leukemia and is associated with worse clinical outcome.

Changes in FLT3 mutation status can occur during the course of disease, but the clinical impact of a change is unclear.

FLT3 is mutated in 30% of acute myeloid leukemia (AML), with internal tandem duplications (ITD) in the juxtamembrane region being the most common.

This results in constitutive activation of FLT3 kinase activity and patients harboring such mutations do not respond well to conventional treatments and demonstrate poor clinical prognosis.

FLT3 mutations are unstable and that there is potential clinical value in continuously monitoring FLT3 mutation status (22684224).

 D324N single-nucleotide polymorphism in the FLT3 gene is associated with higher risk of myeloid leukemias (16320249).

References

 Clinical impact of change of FLT3 mutation status in acute myeloid leukemia patients. Warren M, Luthra R, Yin CC, Ravandi F, Cortes JE, Kantarjian HM, Medeiros LJ, Zuo Z. Mod Pathol. 2012 Jun 8. PMID: 22684224

 Schnittger S, Kohl TM, Leopold N, Schoch C, Wichmann HE, Kern W, Lohse P, Hiddemann W, Haferlach T, Spiekermann K. D324N single-nucleotide polymorphism in the FLT3 gene is associated with higher risk of myeloid leukemias. Genes Chromosomes Cancer. 2006 Apr;45(4):332-7. PMID: 16320249

Reviews

 Stirewalt DL, Radich JP. The role of FLT3 in haematopoietic malignancies. Nat Rev Cancer. 2003 Sep;3(9):650-65. PMID: 12951584

 Abu-Duhier, F. M.; Goodeve, A. C.; Wilson, G. A.; Care, R. S.; Peake, I. R.; Reilly, J. T. : Identification of novel FLT-3 Asp835 mutations in adult acute myeloid leukaemia. Brit. J. Haemat. 113: 983-988, 2001. PubMed ID : 11442493

 Abu-Duhier, F. M.; Goodeve, A. C.; Wilson, G. A.; Gari, M. A.; Peake, I. R.; Rees, D. C.; Vanderberghe, E. A.; Winship, P. R.; Reilly, J. T. : FLT3 internal tandem duplication mutations in adult acute myeloid leukaemia define a high-risk group. Brit. J. Haemat. 111: 190-195, 2000. PubMed ID : 11091200

 Ansari-Lari, M. A.; Yang, C.-F.; Tinawi-Aljundi, R.; Cooper, L.; Long, P.; Allan, R. H.; Borowitz, M. J.; Berg, K. D.; Murphy, K. M. : FLT3 mutations in myeloid sarcoma. Brit. J. Haemat. 126: 785-791, 2004. PubMed ID : 15352981

 Armstrong, S. A.; Mabon, M. E.; Silverman, L. B.; Li, A.; Gribben, J. G.; Fox, E. A.; Sallan, S. E.; Korsmeyer, S. J. : FLT3 mutations in childhood acute lymphoblastic leukemia. Blood 103: 3544-3546, 2004. PubMed ID : 14670924