Myeloid cell differentiation arrest by miR-125b-1 in myelodysplasic syndrome and acute myeloid leukemia with the t(2;11)(p21;q23) translocation
Bousquet, Marina × Quelen, Cathy Rosati, Roberto Mansat-De Mas, Véronique La Starza, Roberta Bastard, Christian Lippert, Eric Talmant, Pascaline Lafage-Pochitaloff, Marina Leroux, Dominique Gervais, Carine Viguié, Franck Lai, Jean-Luc Terre, Christine Beverlo, Berna Sambani, Costantina Hagemeijer-Hausman, Anne Marynen, Peter Delsol, Georges Dastugue, Nicole Mecucci, Cristina Brousset, Pierre #
Rockefeller univ press
Journal of Experimental Medicine vol:205 issue:11 pages:2499-2506
Most chromosomal translocations in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) involve oncogenes that are either up-regulated or form part of new chimeric genes. The t(2; 11)(p21;q23) translocation has been cloned in 19 cases of MDS and AML. In addition to this, we have shown that this translocation is associated with a strong up-regulation of miR-125b (from 6- to 90-fold). In vitro experiments revealed that miR- 125b was able to interfere with primary human CD34(+) cell differentiation, and also inhibited terminal (monocytic and granulocytic) differentiation in HL60 and NB4 leukemic cell lines. Therefore, miR-125b up-regulation may represent a new mechanism of myeloid cell transformation, and myeloid neoplasms carrying the t(2; 11) translocation define a new clinicopathological entity.