TY - JOUR
T1 - Whole exome sequencing identifies novel mutations of epigenetic regulators in chemorefractory pediatric acute myeloid leukemia
AU - Zhan, Di
AU - Zhang, Yingchi
AU - Xiao, Peifang
AU - Zheng, Xinchang
AU - Ruan, Min
AU - Zhang, Jingliao
AU - Chen, Aili
AU - Zou, Yao
AU - Chen, Yumei
AU - Huang, Gang
AU - Hu, Shaoyan
AU - Wang, Qian fei
AU - Zhu, Xiaofan
N1 - Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2018/2
Y1 - 2018/2
N2 - Genomic alterations underlying chemotherapy resistance remains poorly characterized in pediatric acute myeloid leukemia (AML). In this study, we used whole exome sequencing to identify gene mutations associated with chemo-resistance in 44 pediatric AML patients. We identified previously unreported mutations involving epigenetic regulators such as KDM5C, SRIT6, CHD4, and PRPF6 in pediatric AML patients. Despite low prevalence in general pediatric AML, mutations involving epigenetic regulators including splicing factors, were collectively enriched as a group in primary chemo-resistance AML patients. In addition, clonal evolution analysis of secondary chemo-resistance AML patients reveals dominant clone at diagnosis could survive several course of intensified chemotherapy. And gain of new mutations in genes such as MVP, TCF3, SS18, and BCL10, may contribute to chemo-resistance at relapse. These results provide novel insights into the genetic basis of treatment failure in pediatric AML.
AB - Genomic alterations underlying chemotherapy resistance remains poorly characterized in pediatric acute myeloid leukemia (AML). In this study, we used whole exome sequencing to identify gene mutations associated with chemo-resistance in 44 pediatric AML patients. We identified previously unreported mutations involving epigenetic regulators such as KDM5C, SRIT6, CHD4, and PRPF6 in pediatric AML patients. Despite low prevalence in general pediatric AML, mutations involving epigenetic regulators including splicing factors, were collectively enriched as a group in primary chemo-resistance AML patients. In addition, clonal evolution analysis of secondary chemo-resistance AML patients reveals dominant clone at diagnosis could survive several course of intensified chemotherapy. And gain of new mutations in genes such as MVP, TCF3, SS18, and BCL10, may contribute to chemo-resistance at relapse. These results provide novel insights into the genetic basis of treatment failure in pediatric AML.
KW - Epigenetic regulator mutations
KW - Pediatric leukemia
KW - Primary chemo-resistance
KW - Whole exome sequencing
UR - http://www.scopus.com/inward/record.url?scp=85038899714&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85038899714&partnerID=8YFLogxK
U2 - 10.1016/j.leukres.2017.12.001
DO - 10.1016/j.leukres.2017.12.001
M3 - Letter
C2 - 29253671
AN - SCOPUS:85038899714
SN - 0145-2126
VL - 65
SP - 20
EP - 24
JO - Leukemia Research
JF - Leukemia Research
ER -