The Journal of Experimental Medicine
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Published online
doi:10.1084/jem.20080285
The Journal of Experimental Medicine, Vol. 205, No. 11, 2499-2506
The Rockefeller University Press, 0022-1007 $30.00
© Bousquet et al.
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BRIEF DEFINITIVE REPORT

 Myeloid cell differentiation arrest by miR-125b-1 in myelodysplasic syndrome and acute myeloid leukemia with the t(2;11)(p21;q23) translocation

Marina Bousquet1, Cathy Quelen1, Roberto Rosati2, Véronique Mansat-De Mas1,3,4, Roberta La Starza2, Christian Bastard5, Eric Lippert6, Pascaline Talmant7, Marina Lafage-Pochitaloff8, Dominique Leroux9, Carine Gervais10, Franck Viguié11, Jean-Luc Lai12, Christine Terre13, Berna Beverlo14, Costantina Sambani15, Anne Hagemeijer16, Peter Marynen16, Georges Delsol1,3,4, Nicole Dastugue1,4, Cristina Mecucci2, and Pierre Brousset1,3,4

1 Institut National de la Santé et de la Recherche Médicale, U563, Centre de Physiopathologie de Toulouse-Purpan, 31300 Toulouse, France
2 Cytogenetic and Molecular Genetic Unit, Division of Hematology, IBiT Foundation, University of Perugia, 06123 Perugia, Italy
3 Université Paul Sabatier, 31062 Toulouse, France
4 Département de Pathologie et d'Hématologie Biologique, Centre Hospitalier Universitaire Purpan, 31059 Toulouse, France
5 Département de Génétique, Centre Henri Becquerel, 76038 Rouen, France
6 Laboratoire d'Hématologie-Cytogénétique, Hôpital Haut-Lévêque, 33604 Pessac, France
7 Laboratoire de Cytogénétique Hématologique, Hôtel Dieu, 44035 Nantes, France
8 Laboratoire de Cytogénétique Hématologique, Centre Hospitalier Universitaire La Timone, 13005 Marseille, France
9 Laboratoire d'Hématologie Cellulaire et Moléculaire, Site Etablissement Français du Sang–Centre Hospitalier Universitaire, 38043 Grenoble, France
10 Laboratoire d'Hématologie Cellulaire et Cytogénétique, Centre Hospitalier Universitaire Haute-Pierre, 67098 Strasbourg, France
11 Laboratoire de Cytogénétique et d'Hématologie Biologique, Hôtel Dieu, 75181 Paris, France
12 Laboratoire de Génétique Médicale, Centre Hospitalier Universitaire, 59037 Lille, France
13 Laboratoire de Cytogénétique et Transfusion Sanguine, BP122, 78150 Le-Chesnay, France
14 Department of Clinical Genetics, Erasmus MC, 3000-3099 Rotterdam, Netherlands
15 Laboratory of Cytogenetics, National Centre of Scientific Research "Demokritos," 10551 Athens, Greece
16 Department of Human Genetics and VIB, Katholieke Universiteit Leuven, 3000 Leuven, Belgium

CORRESPONDENCE Pierre Brousset: brousset.p{at}chu-toulouse.fr

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.

C. Quelen and R. Rosati contributed equally to this paper.

© 2008 Bousquet et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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