Virginie Eclache, John Boudjarane, Naïs Prade, Stéphanie Struski, Laetitia Largeaud, Cyril Broccardo, Joop H. Jansen, Christine Terré, Marie-Agnès Collonge-Rame, Pierre-Yves Juvin, Dominique Penther, Stéphanie Lagarde, Antoine Ittel, Véronique Mansat-De Mas, G Ameye, Isabelle Luquet, Marina Lafage-Pochitaloff, Carole Barin, David Rombaut, Bastien Gerby, Carine Gervais, Steven Richebourg, Oliver M. Dovey, Pierre Bories, Christine Lefebvre, Isabelle Radford-Weiss, Audrey Bidet, Isabelle Tigaud, George S. Vassiliou, Benedicte Ribourtout, Tobias Tekath, Michaela Fontenay, Lucienne Michaux, Sylvie Hébrard, Hélène Antoine-Poirel, Laura Jamrog, Vincent Fregona, Nathalie Nadal, Eric Delabesse, Véronique Baccini, Kosuke Yusa, Gerby, Bastien [0000-0002-2657-4200], Baccini, Véronique [0000-0003-3913-7664], Largeaud, Laetitia [0000-0001-5341-5427], Fregona, Vincent [0000-0003-4857-1737], Prade, Naïs [0000-0003-4718-7848], Jamrog, Laura [0000-0003-2288-0806], Mansat-De Mas, Véronique [0000-0003-1878-9129], Dovey, Oliver M [0000-0003-3586-4813], Yusa, Kosuke [0000-0002-3442-021X], Vassiliou, George S [0000-0003-4337-8022], Jansen, Joop H [0000-0001-9459-568X], Tekath, Tobias [0000-0002-9315-5452], Rombaut, David [0000-0001-8910-0945], Ameye, Geneviève [0000-0002-5838-2879], Ittel, Antoine [0000-0001-5067-575X], Michaux, Lucienne [0000-0002-8357-7942], Poirel, Hélène A [0000-0002-0712-5127], Struski, Stéphanie [0000-0002-2282-4364], Fontenay, Michaela [0000-0002-5492-6349], Broccardo, Cyril [0000-0003-3016-6549], Delabesse, Eric [0000-0002-0928-0753], Apollo - University of Cambridge Repository, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Key Points We detail at clinical, cytological, cytogenetic, and molecular levels 113 cases of MDS and MDS/MPN with del(11q), a rare recurrent event.CADM1, a tumor suppressor gene identified initially in solid tumors, ATM, CBL, and KMT2A are deleted and/or mutated in del(11q)., Visual Abstract, Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis leading to peripheral cytopenias and in a substantial proportion of cases to acute myeloid leukemia. The deletion of the long arm of chromosome 11, del(11q), is a rare but recurrent clonal event in MDS. Here, we detail the largest series of 113 cases of MDS and myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN) harboring a del(11q) analyzed at clinical, cytological, cytogenetic, and molecular levels. Female predominance, a survival prognosis similar to other MDS, a low monocyte count, and dysmegakaryopoiesis were the specific clinical and cytological features of del(11q) MDS. In most cases, del(11q) was isolated, primary and interstitial encompassing the 11q22-23 region containing ATM, KMT2A, and CBL genes. The common deleted region at 11q23.2 is centered on an intergenic region between CADM1 (also known as Tumor Suppressor in Lung Cancer 1) and NXPE2. CADM1 was expressed in all myeloid cells analyzed in contrast to NXPE2. At the functional level, the deletion of Cadm1 in murine Lineage-Sca1+Kit+ cells modifies the lymphoid-to-myeloid ratio in bone marrow, although not altering their multilineage hematopoietic reconstitution potential after syngenic transplantation. Together with the frequent simultaneous deletions of KMT2A, ATM, and CBL and mutations of ASXL1, SF3B1, and CBL, we show that CADM1 may be important in the physiopathology of the del(11q) MDS, extending its role as tumor-suppressor gene from solid tumors to hematopoietic malignancies.