Whole exome sequencing identifies novel mutations of epigenetic regulators in chemorefractory pediatric acute myeloid leukemia

Di Zhan, Yingchi Zhang, Peifang Xiao, Xinchang Zheng, Min Ruan, Jingliao Zhang, Aili Chen, Yao Zou, Yumei Chen, Gang Huang, Shaoyan Hu, Qian fei Wang, Xiaofan Zhu

Producción científica: Letterrevisión exhaustiva

23 Citas (Scopus)

Resumen

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.

Idioma originalEnglish (US)
Páginas (desde-hasta)20-24
Número de páginas5
PublicaciónLeukemia Research
Volumen65
DOI
EstadoPublished - feb 2018
Publicado de forma externa

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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