title: Abnormal telomere metabolism in Fanconi's anaemia correlates with genomic instability and the probability of developing severe aplastic anaemia.
abstract: Fanconi's anaemia (FA) is an autosomal recessive disorder characterized by progressive bone marrow failure and a susceptibility to cancer. Haematopoietic stem cell transplantation is the only curative method for restoring normal haematopoiesis, and survival is improved if the transplant is carried out before severe complications occur. However, the evolution of FA is difficult to predict because of the absence of known prognostic factors and the unknown function of the genes involved. In studying 71 FA patients, a correlation was found between severe aplastic anaemia (SAA) and the individual annual telomere-shortening rate (IATSR) in peripheral blood mononuclear cells (P < 10(-3)). Spontaneous apoptosis was highest in SAA patients or patients with high IATSR (> 200 bp/year) (P < 0.01, n = 18). Univariate and multivariate analyses showed that significant relative risks for evolution towards SAA were high IATSR (P < 10(-4)), and that a high number of chromosome breakages occurred in the presence of nitrogen mustard (P < 0.001). A high IATSR was also associated with an increased frequency of malignancy (P < 0.01). Thus, these biological parameters were related to the spontaneous evolution of FA and could be used as prognostic factors. These data indicated that telomeres might play a role in the evolution of bone marrow failure and malignant transformation in FA.
authors.affiliation: Bone Marrow Biology Laboratory, DRED University, Paris, France.
authors.forename: Xiaxin
authors.initials: X
authors.lastname: Li
authors.forename: François
authors.initials: F
authors.lastname: Leteurtre
authors.forename: Vanderson
authors.initials: V
authors.lastname: Rocha
authors.forename: Philippe
authors.initials: P
authors.lastname: Guardiola
authors.forename: Roland
authors.initials: R
authors.lastname: Berger
authors.forename: Marie-Therese
authors.initials: MT
authors.lastname: Daniel
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: Noguera
authors.forename: Odile
authors.initials: O
authors.lastname: Maarek
authors.forename: Gwenaëlle L E
authors.initials: GL
authors.lastname: Roux
authors.forename: Pauline
authors.initials: P
authors.lastname: de la Salmonière
authors.forename: Patrice
authors.initials: P
authors.lastname: Richard
authors.forename: Eliane
authors.initials: E
authors.lastname: Gluckman
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000209:etiology* / Q000473:pathology; D017209:Apoptosis / Q000235:genetics; D001854:Bone Marrow Cells / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D019457:Chromosome Breakage; D005199:Fanconi Anemia / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D007951:Leukemia, Myeloid / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics; D011379:Prognosis; D016615:Telomere / Q000235:genetics / Q000378:metabolism* / Q000473:pathology