Submitted November 17, 2008
Accepted February 19, 2009
Deregulation of micro-RNA involved in hematopoiesis and the immune response in HTLV-I adult T-cell leukemia
Marcia Bellon, Yves Lepelletier, Olivier Hermine, and Christophe Nicot*
University of Kansas Medical Center, Department of Pathology and Laboratory Medicine, Center for Viral Oncology and KUCC, Kansas City, KS, United States
Hopital Necker Universite Paris V, Centre National de la Recherche Scientifique Unite Mixte de Recherche (CNRS UMR) 8147, Paris, France
* Corresponding author; email: cnicot{at}kumc.edu.
Human T cell leukemia virus type-I (HTLV-I) is the etiological agent of Adult T-cell Leukemia (ATL) an aggressive lymphoproliferative disease. MicroRNAs (miRNAs) are differentially expressed during hematopoiesis and lineage commitment of hematopoietic stem cell progenitors (HSCPs). Here, we report aberrant expression of hematopoietic specific miR-223, miR-181a, miR-150, miR-142.3p and miR-155 in HTLV-I infected cells in vitro and uncultured ex vivo ATL cells. Our results suggest that HTLV-I infected cells have an unbalanced expression of miRNA that favor T-cell differentiation. We also found altered expression of miRNA previously recognized as innate immunity regulators: miR-155, miR-125a, miR-132 and miR-146. Strikingly, our data also revealed significant differences between ex vivo ATL tumor cells and in vitro HTLV-I cell lines. Specifically, miR-150 and miR-223 were up-regulated in ATL patients but consistently down-regulated in HTLV-I cell lines suggesting that ATL cells and in vitro established cells are derived from distinct cellular populations.
