The role of FLT3 mutations in the pathogenesis of acute myeloid leukemia

Czech version

Authors: J. Gazdová; D. Dvořáková; I. Ježíšková; F. Rázga; T. Jurček; J. Mayer
Authors‘ workplace: Centrum molekulární biologie a genové terapie, Interní hematoonkologická klinika, FN Brno a LF MU
Published in: Transfuze Hematol. dnes,15, 2009, No. 4, p. 229-236.
Category: Comprehensive Reports, Original Papers, Case Reports

Overview

FLT3 (FMS-like tyrosine kinase 3) is a tyrosine kinase receptor expressed by early hematopoietic progenitor cells and is essential for its normal development and proliferation. Activating mutations of this kinase are found in approximately 40% of all AML cases and are therefore one of the most common genetic alterations observed in AML. Mutations in FLT3 gene lead to constitutive phosphorylation of the receptor and consecutive activation of downstream signalling pathways resulting in uncontrolled cell proliferation. FLT3 mutational status, especially internal tandem duplications in exons 14 and 15, appears to be a significant prognostic indicator associated with a distinctly worse clinical outcome in AML patients with normal cytogenetics in terms of shorter complete remission duration (CRD) and disease free survival (DFS). Prognostic impact of point mutations in tyrosine kinase domain is less clear and is still under debate. High frequency of FLT3 mutations and its prognostic relevance in both adult and pediatric AML makes it an appropriate target for therapy. There are several FLT3 tyrosine kinase inhibitors tested in ongoing preclinical and clinical trials.

Key words:
FLT3 receptor tyrosine kinase, cytogenetically normal AML, internal tandem duplication, prognostic marker

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Article was published in

Transfusion and Haematology Today

2009 Issue 4