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. 2010 Oct;11(10):762-70.
doi: 10.1631/jzus.B1000052.

FLT3 and NPM1 mutations in Chinese patients with acute myeloid leukemia and normal cytogenetics

Lei Wang  1 , Wei-lai Xu, Hai-tao Meng, Wen-bin Qian, Wen-yuan Mai, Hong-yan Tong, Li-ping Mao, Yin Tong, Jie-jing Qian, Yin-jun Lou, Zhi-mei Chen, Yun-gui Wang, Jie Jin
Affiliations

FLT3 and NPM1 mutations in Chinese patients with acute myeloid leukemia and normal cytogenetics

Lei Wang et al. J Zhejiang Univ Sci B. 2010 Oct.

Abstract

Mutations of fms-like tyrosine kinase 3 (FLT3) and nucleophosmin (NPM1) exon 12 genes are the most common abnormalities in adult acute myeloid leukemia (AML) with normal cytogenetics. To assess the prognostic impact of the two gene mutations in Chinese AML patients, we used multiplex polymerase chain reaction (PCR) and capillary electrophoresis to screen 76 AML patients with normal cytogenetics for mutations in FLT3 internal tandem duplication (FLT3/ITD) and exon 12 of the NPM1 gene. FLT3/ITD mutation was detected in 15 (19.7%) of 76 subjects, and NPM1 mutation in 20 (26.3%) subjects. Seven (9.2%) cases were positive for both FLT3/ITD and NPM1 mutations. Significantly more FLT3/ITD aberration was detected in subjects with French-American-British (FAB) M1 (42.8%). NPM1 mutation was frequently detected in subjects with M5 (47.1%) and infrequently in subjects with M2 (11.1%). FLT3 and NPM1 mutations were significantly associated with a higher white blood cell count in peripheral blood and a lower CD34 antigen expression, but not age, sex, or platelet count. Statistical analysis revealed that the FLT3/ITD-positive group had a lower complete remission (CR) rate (53.3% vs. 83.6%). Survival analysis showed that the FLT3/ITD-positive/NPM1 mutation-negative group had worse overall survival (OS) and relapse-free survival (RFS). The FLT3/ITD-positive/NPM1 mutation-positive group showed a trend towards favorable survival compared with the FLT3/ITD-positive/NPM1 mutation-negative group (P=0.069). Our results indicate that the FLT3/ITD mutation might be a prognostic factor for an unfavorable outcome in Chinese AML subjects with normal cytogenetics, while NPM1 mutation may be a favorable prognostic factor for OS and RFS in the presence of FLT3/ITD.

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Figures

Fig. 1
Fig. 1
Capillary gel electrophoresis for FLT3 and NPM1 genes in three cases (a) A case with wide type NPM1 (167 bp) and wide type FLT3 (329 bp); (b) A case with FLT3/ITD positive; (c) A case with NPM1 mutant and FLT3/ITD positive simultaneously
Fig. 1
Fig. 1
Capillary gel electrophoresis for FLT3 and NPM1 genes in three cases (a) A case with wide type NPM1 (167 bp) and wide type FLT3 (329 bp); (b) A case with FLT3/ITD positive; (c) A case with NPM1 mutant and FLT3/ITD positive simultaneously
Fig. 1
Fig. 1
Capillary gel electrophoresis for FLT3 and NPM1 genes in three cases (a) A case with wide type NPM1 (167 bp) and wide type FLT3 (329 bp); (b) A case with FLT3/ITD positive; (c) A case with NPM1 mutant and FLT3/ITD positive simultaneously
Fig. 2
Fig. 2
Distribution of FLT3 (a) and NPM1 (b) mutations in morphologic subtypes * P<0.001, # P<0.05, compared with other FAB subtypes
Fig. 2
Fig. 2
Distribution of FLT3 (a) and NPM1 (b) mutations in morphologic subtypes * P<0.001, # P<0.05, compared with other FAB subtypes
Fig. 3
Fig. 3
Kaplan-Meier analysis results according to the gene mutation status in CN AML patients (a) OS and RFS for FLT3/ITD; (b) OS and RFS for NPM1
Fig. 3
Fig. 3
Kaplan-Meier analysis results according to the gene mutation status in CN AML patients (a) OS and RFS for FLT3/ITD; (b) OS and RFS for NPM1
Fig. 4
Fig. 4
Survival analysis estimates for probabilities of OS (a) and RFS (b) according to the four mutation statuses
Fig. 4
Fig. 4
Survival analysis estimates for probabilities of OS (a) and RFS (b) according to the four mutation statuses
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