The genomic landscape of hypodiploid acute lymphoblastic leukemia
Details
Publication Year 2013-03, Volume 45, Issue #3, Page 242-252
Journal Title
NATURE GENETICS
Publication Type
Journal 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.
Publisher
NATURE PUBLISHING GROUP
Keywords
JUVENILE MYELOMONOCYTIC LEUKEMIA; NEUROFIBROMATOSIS TYPE-1 GENE; REGULATORY T-CELLS; TRANSMEMBRANE ADAPTER; HEMATOLOGIC MALIGNANCIES; P53 MUTATIONS; HUMAN CANCERS; MUTANT P53; IKAROS; CHILDHOOD
WEHI Research Division(s)
Molecular Medicine; Cancer And Haematology
Publisher's Version
https://doi.org/10.1038/ng.2532
Rights Notice
© 2013 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved


Creation Date: 2013-03-01 12:00:00
Last Modified: 0001-01-01 12:00:00
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