TY - JOUR
T1 - Global microRNA expression profiling uncovers molecular markers for classification and prognosis in aggressive B-cell lymphoma
AU - Iqbal, Javeed
AU - Shen, Yulei
AU - Huang, Xin
AU - Liu, Yanyan
AU - Wake, Laura
AU - Liu, Cuiling
AU - Deffenbacher, Karen
AU - Lachel, Cynthia M.
AU - Wang, Chao
AU - Rohr, Joseph
AU - Guo, Shuangping
AU - Smith, Lynette M.
AU - Wright, George
AU - Bhagavathi, Sharathkumar
AU - Dybkaer, Karen
AU - Fu, Kai
AU - Greiner, Timothy C.
AU - Vose, Julie M.
AU - Jaffe, Elaine
AU - Rimsza, Lisa
AU - Rosenwald, Andreas
AU - Ott, German
AU - Delabie, Jan
AU - Campo, Elias
AU - Braziel, Rita M.
AU - Cook, James R.
AU - Tubbs, Raymond R.
AU - Armitage, James O.
AU - Weisenburger, Dennis D.
AU - Staudt, Louis M.
AU - Gascoyne, Randy D.
AU - McKeithan, Timothy W.
AU - Chan, Wing C.
N1 - Publisher Copyright:
Copyright 2011 by The American Society of Hematology. All rights reserved.
PY - 2015/2/12
Y1 - 2015/2/12
N2 - 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 avianmyelomatosis viral oncogene homolog(MYC) targets and enabled the differentiation ofBLfromDLBCL, a distinction comparable with the "gold standard" GEP-defined diagnosis. Distinct miRNA signatures were identified for DLBCL subgroups, includingGCB-DLBCL,activatedB-cell (ABC)-DLBCL, andPMBL. Interestingly, most of the unclassifiable-DLBCL byGEP 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.
AB - 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 avianmyelomatosis viral oncogene homolog(MYC) targets and enabled the differentiation ofBLfromDLBCL, a distinction comparable with the "gold standard" GEP-defined diagnosis. Distinct miRNA signatures were identified for DLBCL subgroups, includingGCB-DLBCL,activatedB-cell (ABC)-DLBCL, andPMBL. Interestingly, most of the unclassifiable-DLBCL byGEP 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.
UR - http://www.scopus.com/inward/record.url?scp=84923308188&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84923308188&partnerID=8YFLogxK
U2 - 10.1182/blood-2014-04-566778
DO - 10.1182/blood-2014-04-566778
M3 - Article
C2 - 25498913
AN - SCOPUS:84923308188
SN - 0006-4971
VL - 125
SP - 1137
EP - 1145
JO - Blood
JF - Blood
IS - 7
ER -