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Blood. 2015 Apr 23;125(17):2669-77. doi: 10.1182/blood-2014-06-584193. Epub 2015 Mar 3.

miR-18b overexpression identifies mantle cell lymphoma patients with poor outcome and improves the MIPI-B prognosticator.

Author information

1
Department of Hematology and.
2
Department of Hematology and Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark;
3
Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark; Center for non-coding RNA in Technology and Health, Department of Health Sciences, University of Copenhagen, Copenhagen, Denmark;
4
Department of Immunotechnology, CREATE Health, Lund University, Lund, Sweden;
5
Departments of Oncology and Pathology, Rikshospitalet, Oslo, Norway;
6
Department of Oncology, Skåne University Hospital, Lund, Sweden;
7
Department of Oncology, Uppsala University Hospital, Uppsala, Sweden;
8
Departments of Hematology and Oncology, Helsinki University Central Hospital, Helsinki, Finland;
9
Department of Pathology, Skåne University Hospital, Lund, Sweden;
10
Department of Immunology, Genetics, and Pathology, Uppsala University Hospital, Uppsala, Sweden;
11
Department of Pathology, Laboratory Diagnostics, Helsinki University Central Hospital, Helsinki, Finland; and.
12
Department of Pathology, Division of Cancer Medicine and Surgery, Oslo University Hospital, Oslo, Norway.
13
Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark;

Abstract

Recent studies show that mantle cell lymphoma (MCL) express aberrant microRNA (miRNA) profiles; however, the clinical effect of miRNA expression has not previously been examined and validated in large prospective homogenously treated cohorts. We performed genome-wide miRNA microarray profiling of 74 diagnostic MCL samples from the Nordic MCL2 trial (screening cohort). Prognostic miRNAs were validated in diagnostic MCL samples from 94 patients of the independent Nordic MCL3 trial (validation cohort). Three miRNAs (miR-18b, miR-92a, and miR-378d) were significantly differentially expressed in patients who died of MCL in both cohorts. MiR-18b was superior to miR-92a and miR-378d in predicting high risk. Thus, we generated a new biological MCL International Prognostic Index (MIPI-B)-miR prognosticator, combining expression levels of miR-18b with MIPI-B data. Compared to the MIPI-B, this prognosticator improved identification of high-risk patients with regard to cause-specific, overall, and progression-free survival. Transfection of 2 MCL cell lines with miR-18b decreased their proliferation rate without inducing apoptosis, suggesting that miR-18b may render MCL cells resistant to chemotherapy by decelerating cell proliferation. We conclude that overexpression of miR-18b identifies patients with poor prognosis in 2 large prospective MCL cohorts and adds prognostic information to the MIPI-B. MiR-18b may reduce the proliferation rate of MCL cells as a mechanism of chemoresistance.

PMID:
25736311
DOI:
10.1182/blood-2014-06-584193
[Indexed for MEDLINE]
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