4.6 Review

Hematopoietic cell transplantation and gene therapy for Diamond-Blackfan anemia: state of the art and science

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An RPS19-edited model for Diamond-Blackfan anemia reveals TP53-dependent impairment of hematopoietic stem cell activity

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Summary: Diamond-Blackfan anemia (DBA) is a genetic blood disease caused by heterozygous loss-of-function mutations in ribosomal protein genes, resulting in hypoplastic anemia and later multilineage cytopenias. A tractable experimental model of DBA was created through genome editing of human HSPCs, revealing associated hematopoietic stem cell defects in the disease.

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Summary: Diamond Blackfan anemia (DBA), a rare bone marrow failure syndrome, is associated with an increased risk of developing cancers, particularly colorectal cancer and osteogenic sarcoma. The challenge lies in providing optimal therapy for these patients due to their bone marrow failure, which may result in poor outcomes. Therefore, implementing rational screening and surveillance strategies is crucial.

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Studies of a mosaic patient with DBA and chimeric mice reveal erythroid cell-extrinsic contributions to erythropoiesis

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Summary: This study follows a patient with Diamond-Blackfan anemia (DBA) and discovers that eltrombopag (EPAG) not only improves her anemia but also maintains the mosaicism. Further experiments using DBA mice and mice lacking a heme export protein support the hypothesis that excess heme in ribosomal protein-deficient erythroid cells inhibits the growth of adjacent normal precursors. The findings have implications for DBA gene therapy and provide insights into anemia in del(5q) myelodysplastic syndrome patients.

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Summary: This study retrospectively compared the outcomes of DBA patients undergoing HSCT with MAC or RIC conditioning regimens. All 27 patients who underwent HSCT successfully engrafted, with a 3-year overall survival rate of 95.2% and a failure-free survival rate of 88.4%, showing no significant differences between MAC and RIC regimens.

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