학술논문
The CADM1tumor suppressor gene is a major candidate gene in MDS with deletion of the long arm of chromosome 11
Document Type
Article
Author
Lafage-Pochitaloff, Marina; Gerby, Bastien; Baccini, Véronique; Largeaud, Laetitia; Fregona, Vincent; Prade, Naïs; Juvin, Pierre-Yves; Jamrog, Laura; Bories, Pierre; Hébrard, Sylvie; Lagarde, Stéphanie; Mansat-De Mas, Véronique; Dovey, Oliver M.; Yusa, Kosuke; Vassiliou, George S.; Jansen, Joop H.; Tekath, Tobias; Rombaut, David; Ameye, Geneviève; Barin, Carole; Bidet, Audrey; Boudjarane, John; Collonge-Rame, Marie-Agnès; Gervais, Carine; Ittel, Antoine; Lefebvre, Christine; Luquet, Isabelle; Michaux, Lucienne; Nadal, Nathalie; Poirel, Hélène A.; Radford-Weiss, Isabelle; Ribourtout, Bénédicte; Richebourg, Steven; Struski, Stéphanie; Terré, Christine; Tigaud, Isabelle; Penther, Dominique; Eclache, Virginie; Fontenay, Michaela; Broccardo, Cyril; Delabesse, Eric
Source
Blood Advances; January 2022, Vol. 6 Issue: 2 p386-398, 13p
Subject
Language
ISSN
24739529; 24739537
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 CBLgenes. 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. CADM1was 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 CBLand mutations of ASXL1, SF3B1, and CBL, we show that CADM1may be important in the physiopathology of the del(11q) MDS, extending its role as tumor-suppressor gene from solid tumors to hematopoietic malignancies.