FLT3 Gene

FLT3 (Fms Related Receptor Tyrosine Kinase 3) is a protein coding gene located on chromosome 13q12.2. The FLT3 gene encodes an important class III receptor tyrosine kinase that is essential for the normal functioning of the myeloid cell as well as for leukemogenesis. The activated receptor kinase phosphorylates and activates several cytoplasmic effector molecules in signaling pathways involved in apoptosis, proliferation and differentiation of hematopoietic cells in the bone marrow (Medinger M et al. 2017).

Mutations of the FLT3 gene leading to constitutive activation of this receptor are detected in acute myeloid leukemia and acute lymphoblastic leukemia (Krstovski N et al. 2010). Related signaling pathways include CNTF and ERK signaling pathways. An important paralog of this gene is FLT1.

An increasing number of inhibitors against the FLT3 kinase have been developed in recent years, some of which have already been approved for the treatment of AML - one each for first-line therapy and for the relapse situation. Therefore, molecular genetic testing for the presence of FLT3 mutations is obligatory at diagnosis and relapse of AML, because patients may benefit from the use of these drugs in case of a positive result. Intensive work is being done on further FLT3 inhibitors as well as on combinations of such substances with chemotherapy or with other targeted therapeutics.

1. Krstovski N et al. (2010) Incidence of FLT3 and nucleophosmin gene mutations in childhood acute myeloid leukemia: Serbian experience and the review of the literature. Med Oncol 27:640-645.
2. Medinger M et al (2017) Acute myeloid leukaemia genomics. Br J Haematol. 2017 Nov;179(4):530-542.