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.
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.
Sritana
Narongrit
N
Chulabhorn Cancer Centre, Chulabhorn Research Institute, Bangkok, Thailand.
Auewarakul
Chirayu U
CU
D017677:Age Distribution; D001483:Base Sequence; D020732:Cytogenetic Analysis; D004252:DNA Mutational Analysis; D005838:Genotype; D006801:Humans; D015994:Incidence; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D013785:Thailand / Q000453:epidemiology; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
D019009:Proto-Oncogene Proteins c-kit; D051941:fms-Like Tyrosine Kinase 3