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International Journal of Hematology

, Volume 83, Issue 4, pp 301–308 | Cite as

Biology, Clinical Relevance, and Molecularly Targeted Therapy in Acute Leukemia with Flt3 Mutation

  • Hitoshi Kiyoi
  • Tomoki Naoe
Progress in Hematology

Abstract

Overexpression and activating mutations of receptor tyrosine kinases (RTKs) are known to be involved in the pathophys-iology of several kinds of cancer cells. FMS-like receptor tyrosine kinase 3 (FLT3), together with KIT, FMS, and platelet-derived growth factor receptor, is a class III RTK. FLT3 mutations were first reported as internal tandem duplication (FLT3/ ITD) of the juxtamembrane domain-coding sequence; subsequently, a missense point mutation at the D835 residue and point mutations, deletions, and insertions in the codons surrounding D835 within a FLT3 tyrosine kinase domain (FLT3/KDMs) have been found. FLT3 mutations are the most frequent genetic alterations so far reported in acute myeloid leukemia and are involved in the signaling pathway of autonomous proliferation and differentiation block in leukemia cells. Several large-scale studies have confirmed that FLT3/ITD is strongly associated with leukocytosis and a poor prognosis.Therefore, routine screening for FLT3 mutations is recommended to stratify patients into distinct risk groups. However, because high-dose chemotherapy and stem cell transplantation cannot overcome the adverse effects of FLT3 mutations, the development of FLT3 kinase inhibitors is expected to produce a more efficacious therapeutic strategy for leukemia therapy.

Key words

FLT3 Mutations Receptor tyrosine kinase Leukemia Molecular target 

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Copyright information

© The Japanese Society of Hematology 2006

Authors and Affiliations

  1. 1.Department of Infectious DiseasesNagoya University School of MedicineNagoyaJapan
  2. 2.Departments of Hematology/OncologyNagoya University Graduate School of MedicineNagoyaJapan

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