| Subnetwork-based analysis of chronic lymphocytic leukemia identifies pathways that associate with disease progression. | |
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MedLine Citation:
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PMID: 22837534 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The clinical course of patients with chronic lymphocytic leukemia (CLL) is heterogeneous. Several prognostic factors have been identified that can stratify patients into groups that differ in their relative tendency for disease progression and/or survival. Here, we pursued a subnetwork-based analysis of gene expression profiles to discriminate between groups of patients with disparate risks for CLL progression. From an initial cohort of 130 patients, we identified 38 prognostic subnetworks that could predict the relative risk for disease progression requiring therapy from the time of sample collection, more accurately than established markers. The prognostic power of these subnetworks then was validated on 2 other cohorts of patients. We noted reduced divergence in gene expression between leukemia cells of CLL patients classified at diagnosis with aggressive versus indolent disease over time. The predictive subnetworks vary in levels of expression over time but exhibit increased similarity at later time points before therapy, suggesting that degenerate pathways apparently converge into common pathways that are associated with disease progression. As such, these results have implications for understanding cancer evolution and for the development of novel treatment strategies for patients with CLL. |
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Authors:
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Han-Yu Chuang; Laura Rassenti; Michelle Salcedo; Kate Licon; Alexander Kohlmann; Torsten Haferlach; Robin Foà; Trey Ideker; Thomas J Kipps |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2012-07-26 |
Journal Detail:
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Title: Blood Volume: 120 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-09-28 Completed Date: 2013-01-10 Revised Date: 2013-05-06 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 2639-49 Citation Subset: AIM; IM |
Affiliation:
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Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA 92093, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Disease Progression Gene Expression Profiling* Gene Regulatory Networks Humans Leukemia, Lymphocytic, Chronic, B-Cell / genetics*, mortality, pathology* Oligonucleotide Array Sequence Analysis Prognosis RNA, Messenger / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction Signal Transduction* Survival Rate Tumor Cells, Cultured Tumor Markers, Biological / genetics*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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ES14811/ES/NIEHS NIH HHS; P01-CA081534/CA/NCI NIH HHS; R37-CA049870/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; 0/Tumor Markers, Biological |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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