The genomic landscape of hypodiploid acute lymphoblastic leukemia

Holmfeldt, L., Wei, L., Diaz-Flores, E., Walsh, M., Zhang, J., Ding, L., Payne-Turner, D., Churchman, M., Andersson A., Chen, S.-C., Mccastlain, K., Becksfort, J., Ma, J., Wu, G., Patel, S.N., Heatley, S.L., Phillips, L.A., Song, G., Easton, J., Parker, M., Chen, X., Rusch, M., Boggs, K., Vadodaria, B., Hedlund, E., Drenberg, C., Baker, S., Pei, D., Cheng, C., Huether, R., Lu, C., Fulton, R.S., Fulton, L.L., Tabib, Y., Dooling, D.J., Ochoa, K., Minden, M., Lewis, I.D., To, L.B., Marlton, P., Roberts, A.W., Raca, G., Stock, W., Neale, G., Drexler, H.G., Dickins, R.A., Ellison, D.W., Shurtleff, S.A., Pui, C.-H., Ribeiro, R.C., Devidas, M., Carroll, A.J., Heerema, N.A., Wood, B., Borowitz ,M.J., Gastier-Foster, J.M., Raimondi, S.C., Mardis, E.R., Wilson, R.K., Downing, J.R., Hunger, S.P., Loh, M.L. and Mullighan, C.G. (2013) The genomic landscape of hypodiploid acute lymphoblastic leukemia. Nature Genetics, 45 3: 242-252. doi:10.1038/ng.2532

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Author Holmfeldt, L.
Wei, L.
Diaz-Flores, E.
Walsh, M.
Zhang, J.
Ding, L.
Payne-Turner, D.
Churchman, M.
Andersson A.
Chen, S.-C.
Mccastlain, K.
Becksfort, J.
Ma, J.
Wu, G.
Patel, S.N.
Heatley, S.L.
Phillips, L.A.
Song, G.
Easton, J.
Parker, M.
Chen, X.
Rusch, M.
Boggs, K.
Vadodaria, B.
Hedlund, E.
Drenberg, C.
Baker, S.
Pei, D.
Cheng, C.
Huether, R.
Lu, C.
Fulton, R.S.
Fulton, L.L.
Tabib, Y.
Dooling, D.J.
Ochoa, K.
Minden, M.
Lewis, I.D.
To, L.B.
Marlton, P.
Roberts, A.W.
Raca, G.
Stock, W.
Neale, G.
Drexler, H.G.
Dickins, R.A.
Ellison, D.W.
Shurtleff, S.A.
Pui, C.-H.
Ribeiro, R.C.
Devidas, M.
Carroll, A.J.
Heerema, N.A.
Wood, B.
Borowitz ,M.J.
Gastier-Foster, J.M.
Raimondi, S.C.
Mardis, E.R.
Wilson, R.K.
Downing, J.R.
Hunger, S.P.
Loh, M.L.
Mullighan, C.G.
Title The genomic landscape of hypodiploid acute lymphoblastic leukemia
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1061-4036
1546-1718
Publication date 2013-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.1038/ng.2532
Volume 45
Issue 3
Start page 242
End page 252
Total pages 11
Place of publication New York, NY, U.S.A.
Publisher Nature Publishing Group
Language eng
Subject 1311 Genetics
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.
Keyword Genetics & Heredity
Genetics & Heredity
GENETICS & HEREDITY
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID RC4CA156329
CA21765
CA98543
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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Created: Sun, 02 Feb 2014, 21:48:27 EST by Matthew Lamb on behalf of School of Medicine