MicroRNAs in mantle cell lymphoma

Abstract

Mantle cell lymphoma (MCL) is a rare and aggressive subtype of non-Hodgkin lymphoma. New treatment modalities, including intensive induction regimens with immunochemotherapy and autologous stem cell transplant, have improved survival. However, many patients still relapse, and there is a need for novel therapeutic strategies. Recent progress has been made in the understanding of the role of microRNAs (miRNAs) in MCL. Comparisons of tumor samples from patients with MCL with their normal counterparts (naive B-cells) have identified differentially expressed miRNAs with roles in cellular growth and survival pathways, as demonstrated in various biological model systems. In addition, MCL clinico-pathological and prognostic subtypes can be identified using individual miRNAs or miRNA classifiers. miRNA based therapies have now shown efficacy in animal models, and many efforts are currently being made to further develop these drugs for use in patients. Thus, there is hope that specific targeting of pathogenic miRNAs may be used in cases of MCL when conventional therapies fail. Here, we review the current knowledge about the role of miRNAs in MCL, and highlight the perspectives for clinical use.

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

“…16,17 In the current study of two similar MCL trial cohorts, we find that the miR-18b expression level significantly adds prognostic information to the MIPI-B approach. By generating a new prognosticator, the MIPI-B-miR, we were able to predict survival of MCL patients after high-dose immunochemotherapy and ASCT and improve the gold standard prognosticator MIPI-B.…”

“…The prognostic impact of miRNAs have previously been studied in MCL, but mainly in smaller, heterogeneous cohorts, treated by variant regimens 16,17 These studies have suggested a number of prognostic miRNAs including miR-18b, 29 and the entire miR-17~92a cluster. However, no other study identified miR-92a as a key component.…”

“…Previous studies have identified various miRNAs that predict outcome in heterogeneous cohorts of MCL patients, 16,17 however, the prognostic value of miRNA profiles in similarly treated cohorts of MCL patients remains to be demonstrated. To evaluate the prognostic performance of the differentially expressed miRNAs we performed mRMR analysis and a leave-one-out crossvalidation using linear discriminant analysis (LDA).…”

“…16,17 Furthermore, the knockdown of specific miRNAs in two MCL-mouse models has demonstrated efficacy in inhibiting lymphoma growth. 18,19 However, there has been only modest consistency between the clinical studies, and at this point, miRNA expression in MCL has not yet been examined in large, prospective, uniformly treated patient cohorts.…”

Epigenetic silencing of miR-26A1 in chronic lymphocytic leukemia and mantle cell lymphoma: Impact on EZH2 expression

“…5 A number of studies have subsequently revealed the biological and clinical relevance of different miRNAs in various types of cancer, including CLL and the clinically more aggressive mantle cell lymphoma (MCL). [6][7][8][9][10][11] One of these miRNAs, miR26A1, was reported to be deregulated in several cancer types, such as thyroid anaplastic carcinoma, Burkitt lymphoma, and rhabdomyosarcoma, and was proposed to function as a tumor suppressor miRNA. [12][13][14] miR26A1 is known to be involved in several key signaling pathways (e.g., p53, TGF-b signaling) and to regulate several transformation-related targets, such as SMAD1 15 and EZH2.…”