title: Bone marrow microenvironment in fanconi anemia: a prospective functional study in a cohort of fanconi anemia patients.
abstract: Fanconi anemia (FA) is a rare condition due to the genetic inactivation of the FA/BRCA pathway. During childhood, most FA patients display progressive bone marrow failure (BMF), the mechanism of which has not been clarified to date. We analyzed BM mesenchymal stem cells (MSCs) from a series of 20 FA patients with BMF (patient median age 12.5 years old, range 7-34). Expression of FANCD2 and sensitivity to mitomycin C, differentiation capacities, and hematopoiesis-supporting abilities, as well as proliferation, cell senescence, and telomere length were assessed. FA MSCs demonstrated hypersensitivity to mitomycin C compared to control MSCs, as expected for FA cells. FA MSCs had normal immunophenotype, support long-term culture of hematopoietic stem cells (HSCs), and display normal differentiation capacities. Telomere loss during cell aging was similar for FA and control MSCs. However, FA MSCs showed reduced long-term proliferation ability, higher stem cell factor and interleukin-6 levels, and increased expression of senescent-associated beta-galactosidase compared to normal MSCs, suggesting a potential role of the BM microenvironment in long-term BMF.
authors: Cell Therapy Unit, Assistance Publique-Hôpitaux de Paris, Saint-Louis Hospital, University Paris, Paris, France.
authors: Séverine
authors: S
authors: Lecourt
authors: Valérie
authors: V
authors: Vanneaux
authors: Thierry
authors: T
authors: Leblanc
authors: Gwenaelle
authors: G
authors: Leroux
authors: Brigitte
authors: B
authors: Ternaux
authors: Marc
authors: M
authors: Benbunan
authors: Christine
authors: C
authors: Chomienne
authors: Andé
authors: A
authors: Baruchel
authors: Jean-Pierre
authors: JP
authors: Marolleau
authors: Eliane
authors: E
authors: Gluckman
authors: Gerard
authors: G
authors: Socié
authors: Jean
authors: J
authors: Soulier
authors: Jérôme
authors: J
authors: Larghero
mesh_terms: D000293:Adolescent; D000328:Adult; D001853:Bone Marrow / Q000473:pathology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence; D002648:Child; D015331:Cohort Studies; D005199:Fanconi Anemia / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D016130:Immunophenotyping; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D019089:Stem Cell Factor / Q000378:metabolism; D016615:Telomere / Q000235:genetics; D055815:Young Adult
chemical_list: C499905:FANCD2 protein, human; D052236:Fanconi Anemia Complementation Group D2 Protein; D015850:Interleukin-6; D019089:Stem Cell Factor