| Literature DB >> 23334668 |
Linda Holmfeldt1, Lei Wei, Ernesto Diaz-Flores, Michael Walsh, Jinghui Zhang, Li Ding, Debbie Payne-Turner, Michelle Churchman, Anna Andersson, 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.
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.Entities:
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Year: 2013 PMID： 23334668 PMCID： PMC3919793 DOI： 10.1038/ng.2532
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330