The genomic landscape of core-binding factor acute myeloid leukemias

Forskningsoutput: TidskriftsbidragLetter

Abstract

Acute myeloid leukemia (AML) comprises a heterogeneous group of leukemias frequently defined by recurrent cytogenetic abnormalities, including rearrangements involving the core-binding factor (CBF) transcriptional complex. To better understand the genomic landscape of CBF-AMLs, we analyzed both pediatric (n = 87) and adult (n = 78) samples, including cases with RUNX1-RUNX1T1 (n = 85) or CBFB-MYH11 (n = 80) rearrangements, by whole-genome or whole-exome sequencing. In addition to known mutations in the Ras pathway, we identified recurrent stabilizing mutations in CCND2, suggesting a previously unappreciated cooperating pathway in CBF-AML. Outside of signaling alterations, RUNX1-RUNX1T1 and CBFB-MYH11 AMLs demonstrated remarkably different spectra of cooperating mutations, as RUNX1-RUNX1T1 cases harbored recurrent mutations in DHX15 and ZBTB7A, as well as an enrichment of mutations in epigenetic regulators, including ASXL2 and the cohesin complex. This detailed analysis provides insights into the pathogenesis and development of CBF-AML, while highlighting dramatic differences in the landscapes of cooperating mutations for these related AML subtypes.

Detaljer

Författare
  • Zachary J Faber
  • Xiang Chen
  • Amanda Larson Gedman
  • Kristy Boggs
  • Jinjun Cheng
  • Jing Ma
  • Ina Radtke
  • Jyh-Rong Chao
  • Michael P Walsh
  • Guangchun Song
  • Jinjun Dang
  • Li Dong
  • Yu Liu
  • Robert Huether
  • Zhongling Cai
  • Heather Mulder
  • Gang Wu
  • Michael Edmonson
  • Michael Rusch
  • Chunxu Qu
  • Yongjin Li
  • Bhavin Vadodaria
  • Jianmin Wang
  • Erin Hedlund
  • Xueyuan Cao
  • Donald Yergeau
  • Joy Nakitandwe
  • Stanley B Pounds
  • Sheila Shurtleff
  • Robert S Fulton
  • Lucinda L Fulton
  • John Easton
  • Evan Parganas
  • Ching-Hon Pui
  • Jeffrey E Rubnitz
  • Li Ding
  • Elaine R Mardis
  • Richard K Wilson
  • Tanja A Gruber
  • Charles G Mullighan
  • Richard F Schlenk
  • Peter Paschka
  • Konstanze Döhner
  • Hartmut Döhner
  • Lars Bullinger
  • Jinghui Zhang
  • Jeffery M Klco
  • James R Downing
Enheter & grupper
Externa organisationer
  • St Jude Children´s Research Hospital, Memphis
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Hematologi
Originalspråkengelska
Sidor (från-till)1551–1556
Antal sidor6
TidskriftNature Genetics
Volym48
StatusPublished - 2016 okt 31
PublikationskategoriForskning
Peer review utfördJa