Analysis of FLT3 internal tandem duplication and D835 mutations in Chinese acute leukemia patients

Abstract

Genomic aberrations of Fms-like tyrosine kinase 3 ( FLT3), including internal tandem duplication (ITD) and point mutations, have been demonstrated in 25–30% of adults acute myeloid leukemia (AML) and are markers of poor prognosis. FLT3/ITD and D835 mutations were analyzed in 194 Chinese patients with acute leukemia and myelodysplastic syndromes (MDS) by polymerase chain reaction (PCR). FLT3/ITDs and D835 mutations were found in 25.9 and 6.3% of 143 AML patients, respectively. Two patients showed both ITD and point mutations. Among the FAB subtypes of AML, the rate of FLT3 aberration was significantly higher in M3 and M5. However, neither aberrations was found in 25 patients with acute lymphoblastic leukemia (ALL), 2 acute hybrid leukemia, 17 MDS and 7 chronic myeloid leukemia in blast crisis (CML-BC). FLT3/ITD was associated to leukocytosis and lower complete remission (CR) rate, and was more prevalent in patients with normal karyotype. In contrast, D835 mutation was not associated with leukocytosis or low CR rate. Our results confirm that FLT3 activating mutations also occur in a significant percentage in Chinese AML patients. FLT3/ITD + patients treated with standard induction regimen could achieve lower complete remission rates compared with patients not harboring this defect. Early detection of FLT3 mutations and an intensification of induction therapy might thus be useful for this group of patients to overcome the poor prognosis.