Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase

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Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase. / Wilkes, M. C.; Siva, K.; Chen, J.; Varetti, G.; Youn, M. Y.; Chae, H.; Ek, F.; 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, M.; Flygare, J.; Sakamoto, K. M.

In: Nature Communications, Vol. 11, No. 1, 3344, 2020.

Research output: Contribution to journalArticle

Harvard

Wilkes, MC, Siva, K, Chen, J, Varetti, G, Youn, MY, Chae, H, Ek, F, Olsson, R, Lundbäck, T, Dever, DP, Nishimura, T, Narla, A, Glader, B, Nakauchi, H, Porteus, MH, Repellin, CE, Gazda, HT, Lin, S, Serrano, M, Flygare, J & Sakamoto, KM 2020, 'Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase', Nature Communications, vol. 11, no. 1, 3344. https://doi.org/10.1038/s41467-020-17100-z

APA

Wilkes, M. C., Siva, K., Chen, J., Varetti, G., Youn, M. Y., Chae, H., Ek, F., 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, M., ... Sakamoto, K. M. (2020). Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase. Nature Communications, 11(1), [3344]. https://doi.org/10.1038/s41467-020-17100-z

CBE

Wilkes MC, Siva K, Chen J, Varetti G, Youn MY, Chae H, Ek F, Olsson R, Lundbäck T, Dever DP, Nishimura T, Narla A, Glader B, Nakauchi H, Porteus MH, Repellin CE, Gazda HT, Lin S, Serrano M, Flygare J, Sakamoto KM. 2020. Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase. Nature Communications. 11(1):Article 3344. https://doi.org/10.1038/s41467-020-17100-z

MLA

Vancouver

Author

Wilkes, M. C. ; Siva, K. ; Chen, J. ; Varetti, G. ; Youn, M. Y. ; Chae, H. ; Ek, F. ; 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, M. ; Flygare, J. ; Sakamoto, K. M. / Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase. In: Nature Communications. 2020 ; Vol. 11, No. 1.

RIS

TY - JOUR

T1 - Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase

AU - Wilkes, M. C.

AU - Siva, K.

AU - Chen, J.

AU - Varetti, G.

AU - Youn, M. Y.

AU - Chae, H.

AU - Ek, F.

AU - Olsson, R.

AU - Lundbäck, T.

AU - Dever, D. P.

AU - Nishimura, T.

AU - Narla, A.

AU - Glader, B.

AU - Nakauchi, H.

AU - Porteus, M. H.

AU - Repellin, C. E.

AU - Gazda, H. T.

AU - Lin, S.

AU - Serrano, M.

AU - Flygare, J.

AU - Sakamoto, K. M.

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-020-17100-z

DO - 10.1038/s41467-020-17100-z

M3 - Article

C2 - 32620751

AN - SCOPUS:85087416409

VL - 11

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 3344

ER -