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| Status |
Public on Jan 15, 2013 |
| Title |
The Genetic Basis of Hypodiploid Acute Lymphoblastic Leukemia |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The genetic basis of hypodiploid acute lymphoblastic leukemia (ALL), characterized by aneuploidy and poor outcome, is unknown. Here, using complementary genome-wide profiling approaches, we show that hypodiploid ALL comprises two major subtypes that differ in the severity of aneuploidy, transcriptional profile and submicroscopic genetic alterations. Near haploid cases with 24-31 chromosomes frequently harbor alterations targeting receptor tyrosine kinase- and Ras signaling (71%) and IKZF3 (AIOLOS; 13%). In contrast, low hypodiploid ALL cases with 32-39 chromosomes are characterized by TP53 alterations (88%), almost half of which are present in non-tumor cells, and have alterations of IKZF2 (HELIOS; 53%) and RB1 (41%). Both near haploid and low hypodiploid tumors exhibit activation of Ras and PI3K signaling pathways, and are sensitive to PI3K inhibition, indicating that these drugs should be explored as a new therapeutic strategy for this frequently lethal form of leukemia.
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| Overall design |
Gene expression profiling was performed on 117 single diagnosis tumor samples and one relapse sample [SJHYPO117]. No control or reference samples were included.
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| Contributor(s) |
Holmfeldt L, Diaz-Flores E, Wei L, Zhang J, Ding L, Payne-Turner D, Churchman M, Andersson A, Chen S, McCastlain K, Becksfort J, Ma J, Wu G, Patel SN, Heatley SL, Song G, Easton J, Parker M, Chen X, Rusch M, Boggs K, Hedlund E, Drenberg C, Baker S, Pei D, Cheng C, Fulton RS, Fulton LL, Dooling DJ, Ochoa K, Minden M, Lewis ID, To LB, Marlton P, Raca G, Stock W, Neale G, Drexler HG, Dickins RA, Shurtleff SA, Pui C, Ribeiro RC, Devidas M, Carroll AJ, Heerema NA, Wood B, Borowitz MJ, Gastier-Foster JM, Raimondi SC, Mardis ER, Wilson RK, Downing JR, Hunger SP, Loh ML, Mullighan CG, Phillips LA |
| Citation(s) |
23334668 |
| Submission date |
Jul 17, 2012 |
| Last update date |
Apr 20, 2018 |
| Contact name |
Linda Holmfeldt |
| Organization name |
St. Jude Children's Research Hospital
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| Department |
Pathology
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| Street address |
262 Danny Thomas Place
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| City |
Memphis |
| State/province |
Tennessee |
| ZIP/Postal code |
38105 |
| Country |
USA |
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| Platforms (1) |
| GPL13158 |
[HT_HG-U133_Plus_PM] Affymetrix HT HG-U133+ PM Array Plate |
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| Samples (118)
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| Relations |
| BioProject |
PRJNA170829 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE27237_RAW.tar |
240.0 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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