Browsing by Subject "fanconi anemia"

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    Consensus of German Transplant Centers on Hematopoietic Stem Cell Transplantation in Fanconi Anemia
    (Thieme, 2015) Chao, M. M.; Ebell, W.; Bader, P.; Beier, R.; Burkhardt, B.; Feuchtinger, T.; Handgretinger, R.; Hanenberg, H.; Koehl, U.; Kratz, C.; Kremens, B.; Lang, P.; Meisel, R.; Mueller, I.; Roessig, C.; Sauer, M.; Schlegel, P. G.; Schulz, A.; Strahm, B.; Thol, F.; Sykora, K. W.; Department of Pediatrics, Indiana University School of Medicine
    Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only curative therapy for the severe hematopoietic complications associated with Fanconi anemia (FA). In Germany, it is estimated that 10–15 transplants are performed annually for FA. However, because FA is a DNA repair disorder, standard conditioning regimens confer a high risk of excessive regimen-related toxicities and mortality, and reduced intensity regimens are linked with graft failure in some FA patients. Moreover, development of graft-versus-host disease is a major contributing factor for secondary solid tumors. The relative rarity of the disorder limits HSCT experience at any single center. Consensus meetings were convened to develop a national approach for HSCT in FA. This manuscript outlines current experience and knowledge about HSCT in FA and, based on this analysis, general recommendations reached at these meetings.
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    Leukemia and chromosomal instability in aged Fancc−/− mice
    (Elsevier, 2016-05) Cerabona, Donna; Sun, Zejin; Nalepa, Grzegorz; Department of Pediatrics, IU School of Medicine
    Fanconi anemia (FA) is an inherited disorder of genomic instability associated with high risk of myelodysplasia and acute myeloid leukemia (AML). Young mice deficient in FA core complex genes do not naturally develop cancer, hampering preclinical studies on malignant hematopoiesis in FA. Here we describe that aging Fancc−/− mice are prone to genomically unstable AML and other hematologic neoplasms. We report that aneuploidy precedes malignant transformation during Fancc−/− hematopoiesis. Our observations reveal that Fancc−/− mice develop hematopoietic chromosomal instability followed by leukemia in an age-dependent manner, recapitulating the clinical phenotype of human FA and providing a proof of concept for future development of preclinical models of FA-associated leukemogenesis.