The genomic landscape of hypodiploid acute lymphoblastic leukemia
Author
Summary, in English
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.
Department/s
- Division of Clinical Genetics
- The pathogenetic mechanisms behind MLL-rearranged acute leukemia in infancy
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publishing year
2013
Language
English
Pages
242-252
Publication/Series
Nature Genetics
Volume
45
Issue
3
Document type
Journal article
Publisher
Nature Publishing Group
Topic
- Medical Genetics
Status
Published
Research group
- The pathogenetic mechanisms behind MLL-rearranged acute leukemia in infancy
ISBN/ISSN/Other
- ISSN: 1546-1718