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The genomic landscape of hypodiploid acute lymphoblastic leukemia
- Holmfeldt, Linda (author)
- Wei, Lei (author)
- Diaz-Flores, Ernesto (author)
- show more...
- Walsh, Michael (author)
- Zhang, Jinghui (author)
- Ding, Li (author)
- Payne-Turner, Debbie (author)
- Churchman, Michelle (author)
- Chen, Shann-Ching (author)
- McCastlain, Kelly (author)
- Becksfort, Jared (author)
- Ma, Jing (author)
- Wu, Gang (author)
- Patel, Samir N. (author)
- Heatley, Susan L. (author)
- Phillips, Letha A. (author)
- Song, Guangchun (author)
- Easton, John (author)
- Parker, Matthew (author)
- Chen, Xiang (author)
- Rusch, Michael (author)
- Boggs, Kristy (author)
- Vadodaria, Bhavin (author)
- Hedlund, Erin (author)
- Drenberg, Christina (author)
- Baker, Sharyn (author)
- Pei, Deqing (author)
- Cheng, Cheng (author)
- Huether, Robert (author)
- Lu, Charles (author)
- Fulton, Robert S. (author)
- Fulton, Lucinda L. (author)
- Tabib, Yashodhan (author)
- Dooling, David J. (author)
- Ochoa, Kerri (author)
- Minden, Mark (author)
- Lewis, Ian D. (author)
- To, L. Bik (author)
- Marlton, Paula (author)
- Roberts, Andrew W. (author)
- Raca, Gordana (author)
- Stock, Wendy (author)
- Neale, Geoffrey (author)
- Drexler, Hans G. (author)
- Dickins, Ross A. (author)
- Ellison, David W. (author)
- Shurtleff, Sheila A. (author)
- Pui, Ching-Hon (author)
- Ribeiro, Raul C. (author)
- Devidas, Meenakshi (author)
- Carroll, Andrew J. (author)
- Heerema, Nyla A. (author)
- Wood, Brent (author)
- Borowitz, Michael J. (author)
- Gastier-Foster, Julie M. (author)
- Raimondi, Susana C. (author)
- Mardis, Elaine R. (author)
- Wilson, Richard K. (author)
- Downing, James R. (author)
- Hunger, Stephen P. (author)
- Loh, Mignon L. (author)
- Mullighan, Charles G. (author)
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- (creator_code:org_t)
- 2013-01-20
- 2013
- English.
- In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:3, s. 242-252
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
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- art (subject category)
- ref (subject category)
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- By the author/editor
- Holmfeldt, Linda
- Wei, Lei
- Diaz-Flores, Ern ...
- Walsh, Michael
- Zhang, Jinghui
- Ding, Li
- show more...
- Payne-Turner, De ...
- Churchman, Miche ...
- Andersson, Anna
- Chen, Shann-Chin ...
- McCastlain, Kell ...
- Becksfort, Jared
- Ma, Jing
- Wu, Gang
- Patel, Samir N.
- Heatley, Susan L ...
- Phillips, Letha ...
- Song, Guangchun
- Easton, John
- Parker, Matthew
- Chen, Xiang
- Rusch, Michael
- Boggs, Kristy
- Vadodaria, Bhavi ...
- Hedlund, Erin
- Drenberg, Christ ...
- Baker, Sharyn
- Pei, Deqing
- Cheng, Cheng
- Huether, Robert
- Lu, Charles
- Fulton, Robert S ...
- Fulton, Lucinda ...
- Tabib, Yashodhan
- Dooling, David J ...
- Ochoa, Kerri
- Minden, Mark
- Lewis, Ian D.
- To, L. Bik
- Marlton, Paula
- Roberts, Andrew ...
- Raca, Gordana
- Stock, Wendy
- Neale, Geoffrey
- Drexler, Hans G.
- Dickins, Ross A.
- Ellison, David W ...
- Shurtleff, Sheil ...
- Pui, Ching-Hon
- Ribeiro, Raul C.
- Devidas, Meenaks ...
- Carroll, Andrew ...
- Heerema, Nyla A.
- Wood, Brent
- Borowitz, Michae ...
- Gastier-Foster, ...
- Raimondi, Susana ...
- Mardis, Elaine R ...
- Wilson, Richard ...
- Downing, James R ...
- Hunger, Stephen ...
- Loh, Mignon L.
- Mullighan, Charl ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
- MEDICAL AND HEAL ...
- and Basic Medicine
- and Medical Genetics
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- Nature Genetics
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- Lund University
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