Journal of Experimental Medicine, volume 205, issue 11, pages 2499-2506

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

Marina Bousquet ¹

Cathy Quelen ¹

Roberto Rosati ²

Véronique Mansat-De Mas ^{1, 3, 4}

Roberta La Starza ²

Christian Bastard ⁵

Eric Lippert ⁶

Pascaline Talmant ⁷

Marina Lafage Pochitaloff ⁸

Dominique Leroux ⁹

Carine Gervais ¹⁰

Franck Viguie ¹¹

Jean Luc Lai ¹²

Christine Terré ¹³

Berna Beverlo ¹⁴

Costantina Sambani ¹⁵

Anne Hagemeijer ¹⁶

Peter Marynen ¹⁶

Georges Delsol ^{1, 3, 4}

Nicole Dastugue ^{1, 4}

Cristina Mecucci ²

Pierre Brousset ^{1, 3, 4}

Show full list: 22 authors

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Institut National de la Santé et de la Recherche Médicale, U563, Centre de Physiopathologie de Toulouse-Purpan, 31300 Toulouse, France |

Cytogenetic and Molecular Genetic Unit, Division of Hematology, IBiT Foundation, University of Perugia, 06123 Perugia, Italy |

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 |

Publication type: Journal Article

Publication date: 2008-10-20

Rockefeller University Press

Journal: Journal of Experimental Medicine

scimago Q1

wos Q1

SJR: 6.838

CiteScore: 26.6

Impact factor: 12.6

ISSN: 00221007, 15409538

DOI: 10.1084/jem.20080285

Copy DOI

Immunology

Immunology and Allergy

Abstract

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.

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