The genomic landscape of hypodiploid acute lymphoblastic leukemia

Academic Article

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. © 2013 Nature America, Inc. All rights reserved.
  • Published In

  • Nature Genetics  Journal
  • Digital Object Identifier (doi)

    Author List

  • Holmfeldt L; Wei L; Diaz-Flores E; Walsh M; Zhang J; Ding L; Payne-Turner D; Churchman M; Andersson A; Chen SC
  • Start Page

  • 242
  • End Page

  • 252
  • Volume

  • 45
  • Issue

  • 3