Journal article
Global microRNA expression profiling uncovers molecular markers for classification and prognosis in aggressive B-cell lymphoma
Blood, Vol.125(7), pp.1137-1145
02/12/2015
DOI: 10.1182/blood-2014-04-566778
PMCID: PMC4326773
PMID: 25498913
Abstract
We studied the global microRNA (miRNA) expression in diffuse large B-cell lymphoma (DLBCL; n = 79), Burkitt lymphoma (BL; n = 36), primary mediastinal B-cell lymphoma (PMBL; n = 12), B-cell lines (n = 11), and normal subsets of naïve B cells, centroblasts (CBs), and peripheral blood B cells along with their corresponding gene expression profiles (GEPs). The normal B-cell subsets have well-defined miRNA signatures. The CB miRNA signature was significantly associated with germinal center B-cell (GCB)-DLBCL compared with activated B-cell (ABC)-DLBCL (P = .002). We identified a 27-miRNA signature that included v-myc avian myelomatosis viral oncogene homolog (MYC) targets and enabled the differentiation of BL from DLBCL, a distinction comparable with the "gold standard" GEP-defined diagnosis. Distinct miRNA signatures were identified for DLBCL subgroups, including GCB-DLBCL, activated B-cell (ABC)-DLBCL, and PMBL. Interestingly, most of the unclassifiable-DLBCL by GEP showed a strong similarity to the ABC-DLBCL by miRNA expression profiling. Consistent results for BL and DLBCL subgroup classification were observed in formalin-fixed, paraffin-embedded tissue, making such tests practical for clinical use. We also identified predictive miRNA biomarker signatures in DLBCL, including high expression of miR-155, which is significantly associated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treatment failure. This finding was further supported by the observation that high expression of miR-155 sensitizes cells to v-akt murine thymoma viral oncogene homolog-1 inhibitors in vitro, suggesting a novel treatment option for resistant DLBCL.
Details
- Title: Subtitle
- Global microRNA expression profiling uncovers molecular markers for classification and prognosis in aggressive B-cell lymphoma
- Creators
- Javeed Iqbal - Department of Pathology and Microbiology andYulei Shen - Department of Pathology and Microbiology andXin Huang - Department of Pathology and Microbiology andYanyan Liu - Department of Pathology and Microbiology andLaura Wake - Department of Pathology and Microbiology andCuiling Liu - Department of Pathology and Microbiology andKaren Deffenbacher - Department of Pathology and Microbiology andCynthia M Lachel - Department of Pathology and Microbiology andChao Wang - Department of Pathology and Microbiology andJoseph Rohr - Department of Pathology and Microbiology andShuangping Guo - Department of Pathology and Microbiology andLynette M Smith - College of Public Health, University of Nebraska Medical Center, Omaha, NEGeorge Wright - Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MDSharathkumar Bhagavathi - Department of Pathology and Microbiology andKaren Dybkaer - Department of Hematology, Aalborg University Hospital, Aalborg, DenmarkKai Fu - Department of Pathology and Microbiology andTimothy C Greiner - Department of Pathology and Microbiology andJulie M Vose - Department of Hematology/Oncology, University of Nebraska Medical Center, Omaha, NEElaine Jaffe - Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MDLisa Rimsza - Department of Pathology, University of Arizona, Tucson, AZAndreas Rosenwald - Department of Pathology, University of Wurzburg, Wurzburg, GermanyGerman Ott - Department of Clinical Pathology, Dr Margareta Fischer-Bosch-Institute of Clinical Pharmacology, Robert-Bosch-Hospital, Stuttgart, GermanyJan Delabie - Department of Pathology, the Norwegian Radium Hospital, University of Oslo, Oslo, NorwayElias Campo - Hospital Clinics, University of Barcelona, Barcelona, SpainRita M Braziel - Clinical Pathology, Oregon Health and Science University, Portland, ORJames R Cook - Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OHRaymond R Tubbs - Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OHJames O Armitage - Department of Hematology/Oncology, University of Nebraska Medical Center, Omaha, NEDennis D Weisenburger - Department of Pathology, City of Hope National Medical Center, Duarte, CA; andLouis M Staudt - Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MDRandy D Gascoyne - Center for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, BC, CanadaTimothy W McKeithan - Department of Pathology and Microbiology and Department of Pathology, City of Hope National Medical Center, Duarte, CA; andWing C Chan - Department of Pathology and Microbiology and Department of Pathology, City of Hope National Medical Center, Duarte, CA; and
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.125(7), pp.1137-1145
- Publisher
- United States
- DOI
- 10.1182/blood-2014-04-566778
- PMID
- 25498913
- PMCID
- PMC4326773
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Grant note
- U01 CA157581 / NCI NIH HHS 1U01CA157581-01 / NCI NIH HHS
- Language
- English
- Date published
- 02/12/2015
- Academic Unit
- Pathology
- Record Identifier
- 9984047751602771
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