Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase

Research output: Contribution to journalArticle


title = "Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase",
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.",
author = "Wilkes, {M. C.} and K. Siva and J. Chen and G. Varetti and Youn, {M. Y.} and H. Chae and F. Ek and R. Olsson and T. Lundb{\"a}ck and Dever, {D. P.} and T. Nishimura and A. Narla and B. Glader and H. Nakauchi and Porteus, {M. H.} and Repellin, {C. E.} and Gazda, {H. T.} and S. Lin and M. Serrano and J. Flygare and Sakamoto, {K. M.}",
year = "2020",
doi = "10.1038/s41467-020-17100-z",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",