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https://hdl.handle.net/2440/83450
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Type: | Journal article |
Title: | The genomic landscape of hypodiploid acute lymphoblastic leukemia |
Author: | To, L. |
Citation: | Nature Genetics, 2013; 45(3):242-252 |
Publisher: | Nature Publishing Group |
Issue Date: | 2013 |
ISSN: | 1061-4036 1546-1718 |
Statement of Responsibility: | Linda Holmfeldt ... L Bik To ... et al. |
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. |
Keywords: | Cell Line, Tumor Animals Humans Mice Chromosome Aberrations Aneuploidy Retinoblastoma Protein Treatment Outcome Transplantation, Heterologous Signal Transduction Gene Expression Regulation, Neoplastic Base Sequence Haploidy Mutation Molecular Sequence Data Tumor Suppressor Protein p53 Ikaros Transcription Factor Precursor Cell Lymphoblastic Leukemia-Lymphoma Phosphatidylinositol 3-Kinases |
Rights: | © 2013 Nature America, Inc. All rights reserved. |
DOI: | 10.1038/ng.2532 |
Published version: | http://dx.doi.org/10.1038/ng.2532 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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