The genomic landscape of hypodiploid acute lymphoblastic leukemia

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), a subtype of ALL characterized by aneuploidy and poor outcome, is unknown. Genomic profiling of 124 hypodiploid ALL cases, including whole-genome and exome sequencing of 40 cases, identified two subtypes that differ in the severity of aneuploidy, transcriptional profiles and submicroscopic genetic alterations. Near-haploid ALL with 24-31 chromosomes harbor alterations targeting receptor tyrosine kinase signaling and Ras signaling (71%) and the lymphoid transcription factor gene IKZF3 (encoding AIOLOS; 13%). In contrast, low-hypodiploid ALL with 32-39 chromosomes are characterized by alterations in TP53 (91.2%) that are commonly present in nontumor cells, IKZF2 (encoding HELIOS; 53%) and RB1 (41%). Both near-haploid and low-hypodiploid leukemic cells show activation of Ras-signaling and phosphoinositide 3-kinase (PI3K)-signaling pathways and are sensitive to PI3K inhibitors, indicating that these drugs should be explored as a new therapeutic strategy for this aggressive form of leukemia.

Detaljer

Författare
  • Linda Holmfeldt
  • Lei Wei
  • Ernesto Diaz-Flores
  • Michael Walsh
  • Jinghui Zhang
  • Li Ding
  • Debbie Payne-Turner
  • Michelle Churchman
  • Shann-Ching Chen
  • Kelly McCastlain
  • Jared Becksfort
  • Jing Ma
  • Gang Wu
  • Samir N. Patel
  • Susan L. Heatley
  • Letha A. Phillips
  • Guangchun Song
  • John Easton
  • Matthew Parker
  • Xiang Chen
  • Michael Rusch
  • Kristy Boggs
  • Bhavin Vadodaria
  • Erin Hedlund
  • Christina Drenberg
  • Sharyn Baker
  • Deqing Pei
  • Cheng Cheng
  • Robert Huether
  • Charles Lu
  • Robert S. Fulton
  • Lucinda L. Fulton
  • Yashodhan Tabib
  • David J. Dooling
  • Kerri Ochoa
  • Mark Minden
  • Ian D. Lewis
  • L. Bik To
  • Paula Marlton
  • Andrew W. Roberts
  • Gordana Raca
  • Wendy Stock
  • Geoffrey Neale
  • Hans G. Drexler
  • Ross A. Dickins
  • David W. Ellison
  • Sheila A. Shurtleff
  • Ching-Hon Pui
  • Raul C. Ribeiro
  • Meenakshi Devidas
  • Andrew J. Carroll
  • Nyla A. Heerema
  • Brent Wood
  • Michael J. Borowitz
  • Julie M. Gastier-Foster
  • Susana C. Raimondi
  • Elaine R. Mardis
  • Richard K. Wilson
  • James R. Downing
  • Stephen P. Hunger
  • Mignon L. Loh
  • Charles G. Mullighan
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Medicinsk genetik
Originalspråkengelska
Sidor (från-till)242-252
TidskriftNature Genetics
Volym45
Utgivningsnummer3
StatusPublished - 2013
PublikationskategoriForskning
Peer review utfördJa