TY - JOUR
T1 - Clinical and biological implications of mutational spectrum in acute myeloid leukemia of FAB subtypes M4 and M5
AU - Cheng, Zhiheng
AU - Hu, Kai
AU - Tian, Lei
AU - Dai, Yifeng
AU - Pang, Yifan
AU - Cui, Wei
AU - Zhao, Hongmian
AU - Qin, Tong
AU - Han, Yu
AU - Hu, Ning
AU - Chen, Li
AU - Wang, Chao
AU - Zhang, Yijie
AU - Wu, Depei
AU - Ke, Xiaoyan
AU - Shi, Jinlong
AU - Fu, Lin
N1 - Publisher Copyright:
© 2018 Nature America, Inc., part of Springer Nature.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - The mutational spectrum and molecular characteristics of acute myelomonocytic lineage leukemia, namely acute myeloid leukemia (AML) French-American-British (FAB) subtypes M4 and M5, are largely unknown. In order to explore the mutational spectrum and prognostic factors of FAB-M4 and -M5, next-generation sequencing (NGS) was performed to screen for mutated genes and fusion genes relevant to the pathogenesis of AML. Of the 63 patients enrolled in the study, 60% had more than three mutated genes. NPM1 had the highest mutation frequency, followed by DNMT3A, FLT3, NRAS, RUNX1, and TET2. Univariate analysis suggested that age ≥60 years was an independent factor for both poor event-free survival (EFS) and overall survival (OS, P = 0.009, 0.002, respectively), MYH11-CBFβ was associated with better EFS and OS (P = 0.029, 0.016, respectively). However, multivariate analysis was not able to identify any independent risk factor for survival in the cohort of FAB-M4 and -M5 patients, including peripheral white blood cell count, bone marrow blast percentage, MYH11-CBFβ, FLT3-ITD, mutations in NPM1 and DNMT3A, and allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our study provided new insight into the mutational spectrum and molecular characteristics of FAB-M4 and -M5. The clinical implications of the genetic signature of FAB-M4 and -M5 need to be further elucidated by larger studies.
AB - The mutational spectrum and molecular characteristics of acute myelomonocytic lineage leukemia, namely acute myeloid leukemia (AML) French-American-British (FAB) subtypes M4 and M5, are largely unknown. In order to explore the mutational spectrum and prognostic factors of FAB-M4 and -M5, next-generation sequencing (NGS) was performed to screen for mutated genes and fusion genes relevant to the pathogenesis of AML. Of the 63 patients enrolled in the study, 60% had more than three mutated genes. NPM1 had the highest mutation frequency, followed by DNMT3A, FLT3, NRAS, RUNX1, and TET2. Univariate analysis suggested that age ≥60 years was an independent factor for both poor event-free survival (EFS) and overall survival (OS, P = 0.009, 0.002, respectively), MYH11-CBFβ was associated with better EFS and OS (P = 0.029, 0.016, respectively). However, multivariate analysis was not able to identify any independent risk factor for survival in the cohort of FAB-M4 and -M5 patients, including peripheral white blood cell count, bone marrow blast percentage, MYH11-CBFβ, FLT3-ITD, mutations in NPM1 and DNMT3A, and allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our study provided new insight into the mutational spectrum and molecular characteristics of FAB-M4 and -M5. The clinical implications of the genetic signature of FAB-M4 and -M5 need to be further elucidated by larger studies.
UR - http://www.scopus.com/inward/record.url?scp=85042629715&partnerID=8YFLogxK
U2 - 10.1038/s41417-018-0013-6
DO - 10.1038/s41417-018-0013-6
M3 - Article
C2 - 29491461
AN - SCOPUS:85042629715
SN - 0929-1903
VL - 25
SP - 77
EP - 83
JO - Cancer Gene Therapy
JF - Cancer Gene Therapy
IS - 3-4
ER -