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• W4238328031 startingPage "2032" @default.
• W4238328031 abstract "Fanconi anemia (FA) is a rare autosomal recessive disease, characterized by bone marrow failure and cancer predisposition. So far, 8 complementation groups have been identified, although mutations in FANCA account for the disease in the majority of FA patients. In this study we characterized the hematopoietic phenotype of a Fanca knockout mouse model and corrected the main phenotypic characteristics of the bone marrow (BM) progenitors using retroviral vectors. The hematopoiesis of these animals was characterized by a modest though significant thrombocytopenia, consistent with reduced numbers of BM megakaryocyte progenitors. As observed in other FA models, the hematopoietic progenitors from Fanca−/− mice were highly sensitive to mitomycin C (MMC). In addition, we observed for the first time in a FA mouse model a marked in vitro growth defect ofFanca−/−progenitors, either when total BM or when purified Lin−Sca-1+ cells were subjected to in vitro stimulation. Liquid cultures ofFanca−/−BM that were stimulated with stem cell factor plus interleukin-11 produced low numbers of granulocyte macrophage colony-forming units, contained a high proportion of apoptotic cells, and generated a decreased proportion of granulocyte versus macrophage cells, compared to normal BM cultures. Aiming to correct the phenotype of Fanca−/−progenitors, purified Lin−Sca-1+ cells were transduced with retroviral vectors encoding the enhanced green fluorescent protein (EGFP) gene and human FANCAgenes. Lin−Sca-1+ cells fromFanca−/−mice were transduced with an efficiency similar to that of samples from wild-type mice. More significantly, transductions with FANCA vectors corrected both the MMC hypersensitivity as well as the impaired ex vivo expansion ability that characterized the BM progenitors ofFanca−/−mice." @default.
• W4238328031 created "2022-05-12" @default.
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• W4238328031 date "2002-09-15" @default.
• W4238328031 modified "2023-09-27" @default.
• W4238328031 title "In vitro phenotypic correction of hematopoietic progenitors from Fanconi anemia group A knockout mice" @default.
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• W4238328031 doi "https://doi.org/10.1182/blood.v100.6.2032.h81802002032_2032_2039" @default.
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