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Article Dans Une Revue Blood Advances Année : 2022

The CADM1 tumor suppressor gene is a major candidate gene in MDS with deletion of the long arm of chromosome 11

Marina Lafage-Pochitaloff
  • Fonction : Auteur
Véronique Baccini
Laetitia Largeaud
Vincent Fregona
Naïs Prade
Pierre-Yves Juvin
  • Fonction : Auteur
Laura Jamrog
Pierre Bories
Sylvie Hébrard
  • Fonction : Auteur
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Stéphanie Lagarde
  • Fonction : Auteur
Véronique Mansat-de Mas
Oliver Dovey
Kosuke Yusa
George Vassiliou
Joop Jansen
Tobias Tekath
David Rombaut
Geneviève Ameye
Carole Barin
  • Fonction : Auteur
Audrey Bidet
  • Fonction : Auteur
John Boudjarane
  • Fonction : Auteur
Marie-Agnès Collonge-Rame
  • Fonction : Auteur
Carine Gervais
  • Fonction : Auteur
Antoine Ittel
Christine Lefebvre
  • Fonction : Auteur
Isabelle Luquet
  • Fonction : Auteur
Lucienne Michaux
Nathalie Nadal
  • Fonction : Auteur
Hélène Poirel
Isabelle Radford-Weiss
  • Fonction : Auteur
Bénédicte Ribourtout
  • Fonction : Auteur
Steven Richebourg
  • Fonction : Auteur
Stéphanie Struski
Christine Terré
  • Fonction : Auteur
Isabelle Tigaud
  • Fonction : Auteur
Dominique Penther
  • Fonction : Auteur
Virginie Eclache
Michaela Fontenay
Cyril Broccardo
Eric Delabesse,

Résumé

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.

Dates et versions

hal-03559295 , version 1 (06-02-2022)

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Citer

Bastien Gerby, Marina Lafage-Pochitaloff, Véronique Baccini, Laetitia Largeaud, Vincent Fregona, et al.. The CADM1 tumor suppressor gene is a major candidate gene in MDS with deletion of the long arm of chromosome 11. Blood Advances, 2022, 6 (2), pp.386-398. ⟨10.1182/bloodadvances.2021005311⟩. ⟨hal-03559295⟩
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