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 Blood, 2 April 2009, Vol. 113, No. 14, pp. 3172-3181.
Prepublished online as a Blood First Edition Paper on January 30, 2009; DOI 10.1182/blood-2008-07-170035.

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HEMATOPOIESIS AND STEM CELLS

Functional involvement of RINF, retinoid-inducible nuclear factor (CXXC5), in normal and tumoral human myelopoiesis

Frédéric Pendino1,2, Eric Nguyen2, Inge Jonassen3, Bjarte Dysvik3, Abdulkader Azouz2, Michel Lanotte2, Evelyne Ségal-Bendirdjian2, and Johan R. Lillehaug1

1 Department of Molecular Biology, University of Bergen, Bergen, Norway; 2 Inserm U685, Hôpital Saint-Louis, Institut Universitaire d'Hématologie, Paris, France; and 3 Bergen Center for Computational Science, Bergen, Norway

Retinoids triggers differentiation of acute promyelocytic leukemia (APL) blasts by transcriptional regulation of myeloid regulatory genes. Using a microarray approach, we have identified a novel retinoid-responsive gene (CXXC5) encoding a nuclear factor, retinoid-inducible nuclear factor (RINF), that contains a CXXC-type zinc-finger motif. RINF expression correlates with retinoid-induced differentiation of leukemic cells and with cytokine-induced myelopoiesis of normal CD34+ progenitors. Furthermore, short hairpin RNA (shRNA) interference suggests for this gene a regulatory function in both normal and tumoral myelopoiesis. Interestingly, RINF localizes to 5q31.3, a small region often deleted in myeloid leukemia (acute myeloid leukemia [AML]/myelodysplasia [MDS]) and suspected to harbor one or several tumor suppressor gene.


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