2009.10.01 – Regulation of JAK2 by miR-135a- prognostic impact in classic Hodgkin lymphoma

http://bloodjournal.hematologylibrary.org/cgi/content/short/114/14/2945?rss=1

Blood, 1 October 2009, Vol. 114, No. 14, pp. 2945-2951.

LYMPHOID NEOPLASIA

Regulation of JAK2 by miR-135a: prognostic impact in classic Hodgkin lymphoma

Alfons Navarro1, Tania Diaz1, Antonio Martinez2, Anna Gaya3, Aina Pons1, Bernat Gel4, Carles Codony3, Gerardo Ferrer5, Carmen Martinez3, Emili Montserrat3, and Mariano Monzo1

1 Human Anatomy Unit, Molecular Oncology and Embryology Laboratory, University of Barcelona Medical School, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona; 2 Hematopathology Section, Laboratory of Pathology and 3 Institute of Hematology and Oncology, Hospital Clinic, IDIBAPS, Barcelona; 4 Software Department, Universitat Politecnica de Catalunya, Barcelona; and 5 Institute of Hematology and Oncology, Laboratory of Translational Hematology, Hospital Clinic, IDIBAPS, Barcelona, Spain

The behavior of classic Hodgkin lymphoma (cHL) is determined by both the intrinsic features of the tumor cells and the characteristics of the microenvironment, making the analysis of entire lymph nodes an effective approach to understanding the disease. We examined the influence of our previously reported 25-microRNA signature for cHL on clinical outcome in 89 homogeneously treated cHL patients with a median follow-up of 80 months. Patients with low miR-135a expression had a higher probability of relapse (P = .04) and a shorter disease-free survival (P = .02). Functional analysis of cHL cell lines showed that mature miR-135a levels increased after pre–miR-135a transfection, causing apoptosis and decreased cell growth. Target analysis showed a direct regulation by miR-135a of JAK2, a cytoplasmic tyrosine kinase involved in a specific subset of cytokine receptor signaling pathways. miR-135a–mediated JAK2 down-regulation led to decreased mRNA and protein levels of the antiapoptotic gene Bcl-xL, suggesting a role for Bcl-xL in miR-135a/JAK2–mediated apoptosis. Our findings confirm the critical role of miR-135a in the survival of cHL cells and in the prognosis of cHL patients, indicating that novel treatment approaches targeting miR-135a may potentially benefit these patients.

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