Use of MicroRNA Expression Profiling to Identify Prognostic Subclasses in Mantle Cell Lymphoma: Mir-29 Family as New Prognostic Markers

Patients with mantle cell lymphoma (MCL) are typically older adults with a male predominance and usually present with stage IV disease. Response to chemotherapy usually results in a tumor response but remissions are short. It carries the poorest prognosis among non-Hodgkin’s lymphoma subtypes and the median survival is 3 to 4 years. However, recent clinical observations have identified variable clinical courses of MCL patients: some patients succumb rapidly to the disease, while others have a more chronic course and may not require treatment for prolonged periods of time. Given this clinical heterogeneity, we performed microRNA expression profiling on 34 mantle cell lymphoma (MCL) biopsy specimens to elucidate its pathogenesis and develop prognostic markers for survival of MCL patients. We identified downregulation of 18 miRNAs and upregulation of 22 miRNAs in MCL when compared with normal peripheral blood B lymphocytes, which is closely associated with molecular abnormalities. Furthermore, we found that expression levels of miR-29 family (miR-29a, miR-29b and miR-29c) were inversely correlated with MCL patient survival. A strong correlation between miR-29a, miR-29b and miR-29c values and newly described prognostic index for MCL patients, MIPI is identified. This first microRNA profling in MCL demonstrated that the miR-29a-c could be useful biomarkers for MCL prognosis and aberrant miRNA expression could contribute molecular MCL oncogenesis.