FMS-like tyrosine kinase 3 gene mutation in acute myeloid leukemia detected by denaturing PAGE and its clinical significance / 中国实验血液学杂志

ABSTRACT

The aim of this study was to analyze the frequency of flt3 length mutation (flt3-LM) in de novo acute myeloid leukemia patients and the relationship between flt3-LM and chromosome alterations, FAB subgroups, as well as efficiency of therapy. Genomic DNA was amplified by PCR; 2% agarose gel or 8% denaturing PAGE were used to detect the length mutation of flt3 gene in 99 de novo acute myeloid leukemia patients; karyotyping in 72 AML patients was performed by G banding technique. The results showed that the flt3-LM was detected in 20.2% (20/99) patients by agarose gel electrophoresis, and in 29.9% (29/99) by denaturing PAGE. The flt3-LM was not detected in M(0) (only one patient was available), but flt3-LM occurrence in AML subtypes was as follow in M(2) (9/30), M(3) (6/27), M(4) (4/14), M(5) (7/19), M(6) (3/8) respectively. flt3-LM in patients with normal karyotypes (39.13%) was more prevalent as compared with patients of abnormal karyotype (24.49%), but there was no statistical difference (p > 0.05). The complete remission (CR) rate in flt3-LM positive patients (36.36%) was lower than that in flt3-LM negative patients (62.75%) in the 73 patients (p < 0.05) whose karyotypic detection was performed. The distributions of flt3-LM were observed in 8 out of 40 CR patients, 8 out of 21 PR patients, and 6 out of 12 NR patients. It is concluded that the denaturing PAGE is more sensitive and reliable to detect the flt3-LM. The flt3 mutation represents a common genetic abnormality in AML patients, and the flt3-LM is associated with lower CR rate.