Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

The genomic landscape of hypodiploid acute lymphoblastic leukemia

Holmfeldt, Linda ; Wei, Lei ; Diaz-Flores, Ernesto ; Walsh, Michael ; Zhang, Jinghui ; Ding, Li ; Payne-Turner, Debbie ; Churchman, Michelle ; Andersson, Anna LU orcid and Chen, Shann-Ching , et al. (2013) In Nature Genetics 45(3). p.242-252
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Genetics
volume
45
issue
3
pages
242 - 252
publisher
Nature Publishing Group
external identifiers
  • wos:000315664800007
  • scopus:84874647204
  • pmid:23334668
ISSN
1546-1718
DOI
10.1038/ng.2532
language
English
LU publication?
yes
id
6332181a-ba03-47f1-964a-f5eff38963c6 (old id 3670117)
date added to LUP
2016-04-01 13:41:38
date last changed
2022-04-21 22:53:54
@article{6332181a-ba03-47f1-964a-f5eff38963c6,
  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.}},
  author       = {{Holmfeldt, Linda and Wei, Lei and Diaz-Flores, Ernesto and Walsh, Michael and Zhang, Jinghui and Ding, Li and Payne-Turner, Debbie and Churchman, Michelle and Andersson, Anna and Chen, Shann-Ching and McCastlain, Kelly and Becksfort, Jared and Ma, Jing and Wu, Gang and Patel, Samir N. and Heatley, Susan L. and Phillips, Letha A. and Song, Guangchun and Easton, John and Parker, Matthew and Chen, Xiang and Rusch, Michael and Boggs, Kristy and Vadodaria, Bhavin and Hedlund, Erin and Drenberg, Christina and Baker, Sharyn and Pei, Deqing and Cheng, Cheng and Huether, Robert and Lu, Charles and Fulton, Robert S. and Fulton, Lucinda L. and Tabib, Yashodhan and Dooling, David J. and Ochoa, Kerri and Minden, Mark and Lewis, Ian D. and To, L. Bik and Marlton, Paula and Roberts, Andrew W. and Raca, Gordana and Stock, Wendy and Neale, Geoffrey and Drexler, Hans G. and Dickins, Ross A. and Ellison, David W. and Shurtleff, Sheila A. and Pui, Ching-Hon and Ribeiro, Raul C. and Devidas, Meenakshi and Carroll, Andrew J. and Heerema, Nyla A. and Wood, Brent and Borowitz, Michael J. and Gastier-Foster, Julie M. and Raimondi, Susana C. and Mardis, Elaine R. and Wilson, Richard K. and Downing, James R. and Hunger, Stephen P. and Loh, Mignon L. and Mullighan, Charles G.}},
  issn         = {{1546-1718}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{242--252}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Genetics}},
  title        = {{The genomic landscape of hypodiploid acute lymphoblastic leukemia}},
  url          = {{http://dx.doi.org/10.1038/ng.2532}},
  doi          = {{10.1038/ng.2532}},
  volume       = {{45}},
  year         = {{2013}},
}