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Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase.pdf (2.46 MB)

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2020-07-03

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cc by (c) Wilkes et al., 2020
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/171314

Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase

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Recurs relacionat

https://doi.org/10.1038/s41467-020-17100-z

Resum

Diamond Blackfan Anemia (DBA) is a congenital bone marrow failure syndrome associated with ribosomal gene mutations that lead to ribosomal insufficiency. DBA is characterized by anemia, congenital anomalies, and cancer predisposition. Treatment for DBA is associated with significant morbidity. Here, we report the identification of Nemo-like kinase (NLK) as a potential target for DBA therapy. To identify new DBA targets, we screen for small molecules that increase erythroid expansion in mouse models of DBA. This screen identified a compound that inhibits NLK. Chemical and genetic inhibition of NLK increases erythroid expansion in mouse and human progenitors, including bone marrow cells from DBA patients. In DBA models and patient samples, aberrant NLK activation is initiated at the Megakaryocyte/Erythroid Progenitor (MEP) stage of differentiation and is not observed in non-erythroid hematopoietic lineages or healthy erythroblasts. We propose that NLK mediates aberrant erythropoiesis in DBA and is a potential target for therapy.

Matèries

Talassèmia, Malalties dels ossos, Malalties hereditàries

Matèries (anglès)

Thalassemia, Bone diseases, Genetic disorders

Citació

Col·leccions

Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))
<b>Publicacions de projectes de recerca finançats per la UE</b>

Citació

WILKES, Mark c., SIVA, Kavitha, CHEN, Jun, VARETTI, G., YOUN, M. y., CHAE, H., OLSSON, R., LUNDBÄCK, T., DEVER, D. p., NISHIMURA, T., NARLA, A., GLADER, B., NAKAUCHI, H., PORTEUS, M. h., REPELLIN, C. e., GAZDA, H. t., LIN, S., SERRANO MARUGÁN, Manuel, FLYGARE, J., SAKAMOTO, K. m.. Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase. _Nature Communications_. 2020. Vol. 11. [consulta: 31 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/171314]

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