MicroRNA expression in chronic lymphocytic leukemia developing autoimmune hemolytic anemia

Abstract

Chronic lymphocytic leukemia (CLL) is frequently associated with autoimmune hemolytic anemia (AIHA). However, the mechanisms governing the association between CLL and AIHA are poorly understood. MicroRNAs (miRNAs) have been associated with different clinico-biological forms of CLL and are also known to play a substantial role in autoimmunity. However, there are no studies correlating miRNA expression with the likelihood that patients with CLL will develop AIHA. In this study, we found that malignant B-cells from patients with CLL subsequently developing AIHA present nine down-regulated (i.e. miR-19a, miR-20a, miR-29c, miR-146b-5p, miR-186, miR-223, miR-324-3p, miR-484 and miR-660) miRNAs. Interestingly, two of these miRNAs (i.e. miR-20a and miR-146b-5p) are involved in autoimmune phenomena, and one (i.e. miR-146b-5p) in both autoimmunity and CLL. Furthermore, we demonstrated that miR-146b-5p modulates CD80, a molecule associated with the B–T-cell synapse and in restoration of the antigen presenting cell capacity of CLL cells.

Keywords::

• Chronic lymphocytic leukemia
• autoimmune hemolytic anemia
• miRNAs
• miR-146b-5p and CD80

Acknowledgements

Our thanks to Dr. Pablo Engle and Dr. Ricardo Bastos and their group for their support.

Potential conflict of interest:

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

This work has been supported thanks in part to the Spanish Ministry of Science, Instituto Carlos III, FISS PI080304 and PI040698; Generalitat de Catalunya, 2009SGR1008; and the CLL Global Foundation. G.F. is the recipient of a grant from the Instituto de Salud Carlos III (PFIS). E.M. is the recipient of an August Pi i Sunyer research award. G.F., K.H., C.M., T.B. and E.M. are members of the European Research Initiative on CLL (ERIC).