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On-line Access: 2010-10-05

Received: 2010-02-16

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Journal of Zhejiang University SCIENCE B 2010 Vol.11 No.10 P.762-770


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

Author(s):  Lei Wang, 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

Affiliation(s):  Department of Hematology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; more

Corresponding email(s):   zjuhematology@163.com

Key Words:  Acute myeloid leukemia (AML), Normal cytogenetics, Prognosis, fms-like tyrosine kinase 3 internal tandem duplication (FLT3/ITD), Nucleophosmin (NPM1), Mutation

Lei Wang, 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. FLT3 and NPM1 mutations in Chinese patients with acute myeloid leukemia and normal cytogenetics[J]. Journal of Zhejiang University Science B, 2010, 11(10): 762-770.

@article{title="FLT3 and NPM1 mutations in Chinese patients with acute myeloid leukemia and normal cytogenetics",
author="Lei Wang, 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",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T FLT3 and NPM1 mutations in Chinese patients with acute myeloid leukemia and normal cytogenetics
%A Lei Wang
%A Wei-lai Xu
%A Hai-tao Meng
%A Wen-bin Qian
%A Wen-yuan Mai
%A Hong-yan Tong
%A Li-ping Mao
%A Yin Tong
%A Jie-jing Qian
%A Yin-jun Lou
%A Zhi-mei Chen
%A Yun-gui Wang
%A Jie Jin
%J Journal of Zhejiang University SCIENCE B
%V 11
%N 10
%P 762-770
%@ 1673-1581
%D 2010
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1000052

T1 - FLT3 and NPM1 mutations in Chinese patients with acute myeloid leukemia and normal cytogenetics
A1 - Lei Wang
A1 - Wei-lai Xu
A1 - Hai-tao Meng
A1 - Wen-bin Qian
A1 - Wen-yuan Mai
A1 - Hong-yan Tong
A1 - Li-ping Mao
A1 - Yin Tong
A1 - Jie-jing Qian
A1 - Yin-jun Lou
A1 - Zhi-mei Chen
A1 - Yun-gui Wang
A1 - Jie Jin
J0 - Journal of Zhejiang University Science B
VL - 11
IS - 10
SP - 762
EP - 770
%@ 1673-1581
Y1 - 2010
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1000052

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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