MiRNA expression profile of chronic lymphocytic leukemia patients with 13q deletion

Deletion 13q (13q-) is the most common cytogenetic aberration in chronic lymphocytic leukemia (CLL) and is associated with the most favorable prognosis as the sole cytogenetic abnormality. However, it is heterogeneous whereby CLL patients with higher percentages of 13q- cells (13q-H) have a more aggressive clinical course and a distinct gene expression profile. The microRNA (miRNA) expression profile of CLL gives additional biological and prognostic information, but its expression in 13q- CLL has not been examined in detail. The miRNA expression of clonal B cell lymphocytes (CD19+ cells) of 38 CLL patients and normal B cells of six healthy donors was analyzed. CLL patients with higher percentages of 13q- cells (≥80%) showed a different level of miRNA expression from patients with lower percentages (<80%). Interestingly, miR-143 was downregulated and miR-155 was overexpressed in 13q-H. This deregulation affected important validated target genes involved in apoptosis (BCL2, MDM2, TP53INP1) and proliferation (KRAS, PI3K-AKT signaling), that could lead to decreased apoptosis and increased proliferation in 13q-H patients. This study provides new evidence about the heterogeneity of the 13q deletion in CLL patients, showing that miRNA regulation could be involved in several significant pathways deregulated in CLL patients with a high number of losses in 13q.This work was partially supported by grants from the Spanish Fondo de Investigaciones Sanitarias FIS 09/01543, PI12/00281, PI15/01471, This work was partially supported by grants from the Spanish Fondo de Investigaciones Sanitarias FIS 09/01543, PI12/00281, PI15/01471, Instituto Salud Carlos III (ISCIII), European Regional Development Fund (ERDF) “Una manera de hacer Europa”, Fundación Castellano Leonesa de Hematología y Hemoterapia (FUCALHH 2013), Conserjería de Educación, Junta de Castilla y León (HUS272U13), Proyectos de Investigación del SACYL, Spain: BIO/47/13, GRS 994/A/14, BIO/SA10/14, BIO/SA31/13, GRS 1172/A/15, COST Action EuGESMA (BM0801), Fundación Española de Hematología y Hemoterapia (FEHH) and by a grant (RD12/0036/0069) from the Red Temática de Investigación Cooperativa en Cáncer (RTICC), Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness & European Regional Development Fund (ERDF) “Una manera de hacer Europa”, (Innocampus; CEI-2010-1-0010), and the European Union Seventh Framework Programme [FP7/2007-2013] under Grant Agreement no. 306242-NGS-PTL. MHS is fully supported by an “Ayuda predoctoral de la Junta de Castilla y Leon” by the Fondo Social Europeo (JCYL-EDU/346/2013 Ph.D. scholarship).(ISCIII), European Regional Development Fund (ERDF) “Una manera de hacer Europa”, Fundación Castellano Leonesa de Hematología y Hemoterapia (FUCALHH 2013), Conserjería de Educación, Junta de Castilla y León (HUS272U13), Proyectos de Investigación del SACYL, Spain: BIO/47/13, GRS 994/A/14, BIO/SA10/14, BIO/SA31/13, GRS 1172/A/15, COST Action EuGESMA (BM0801), Fundación Española de Hematología y Hemoterapia (FEHH) and by a grant (RD12/0036/0069) from the Red Temática de Investigación Cooperativa en Cáncer (RTICC), Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness & European Regional Development Fund (ERDF) “Una manera de hacer Europa”, (Innocampus; CEI-2010-1-0010), and the European Union Seventh Framework Programme [FP7/2007-2013] under Grant Agreement no. 306242-NGS-PTL. MHS is fully supported by an “Ayuda predoctoral de la Junta de Castilla y Leon” by the Fondo Social Europeo (JCYL-EDU/346/2013 Ph.D. scholarship).Peer Reviewe