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Title: Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase
Author: 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.
Keywords: Talassèmia
Malalties dels ossos
Malalties hereditàries
Bone diseases
Genetic disorders
Issue Date: 3-Jul-2020
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: Nature Communications, 2020, vol. 11
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Appears in Collections:Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))

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