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. 2008 Dec;85(3):227-31.
doi: 10.1016/j.yexmp.2008.09.004. Epub 2008 Oct 11.

KIT and FLT3 receptor tyrosine kinase mutations in acute myeloid leukemia with favorable cytogenetics: two novel mutations and selective occurrence in leukemia subtypes and age groups

Narongrit Sritana  1 , Chirayu U Auewarakul
Affiliations

KIT and FLT3 receptor tyrosine kinase mutations in acute myeloid leukemia with favorable cytogenetics: two novel mutations and selective occurrence in leukemia subtypes and age groups

Narongrit Sritana et al. Exp Mol Pathol. 2008 Dec.

Abstract

Mutations of the receptor tyrosine kinase (RTK) are frequently reported in acute myeloid leukemia (AML) with a normal karyotype. In this study, Southeast Asian AML patients with a favorable karyotype including t(8;21)/AML-ETO, inv(16)(CBF beta/SMMHC), and t(15;17)/PML-RAR alpha were genotyped for KIT and FLT3 RTK mutations by PCR and sequencing. The combined frequency of KIT/FLT3 mutations in patients with t(8;21), inv(16) and t(15;17) was 35%, 18% and 41%. KIT mutations were mainly detected in patients with t(8;21) (23%) and undetectable in patients with t(15;17). Two novel KIT mutations were identified. FLT3 mutations were preferentially found in patients with t(15;17) (41%). Patients with inv(16) had a strikingly low frequency of both KIT and FLT3 mutations (9% each). KIT-mutated patients were older than FLT3-mutated patients and demonstrated a high expression of myeloid antigens and CD56 lymphoid antigen. FLT3 mutation was coexistent with PML-RAR alpha with markedly low or no CD11c and HLA-DR expression. KIT and FLT3 mutations preferentially exist in distinct clinical and genetic AML subtypes, reflecting unique leukemogenetic mechanisms. Targeting therapy with specific RTK inhibitors should provide benefits for a subgroup of AML patients with favorable chromosomes who also carry selective types of RTK mutations.

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