Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase

Research output: Contribution to journalArticle


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.


  • M. C. Wilkes
  • K. Siva
  • G. Varetti
  • M. Y. Youn
  • H. Chae
  • T. Lundbäck
  • D. P. Dever
  • T. Nishimura
  • A. Narla
  • B. Glader
  • H. Nakauchi
  • M. H. Porteus
  • C. E. Repellin
  • H. T. Gazda
  • S. Lin
  • M. Serrano
  • K. M. Sakamoto
External organisations
  • Stanford University
  • Institute for Research in Biomedicine (IRB Barcelona)
  • Barcelona Institute of Science and Technology
  • Catalan Institution for Research and Advanced Studies
  • Karolinska Institutet
  • University of Tokyo
  • SRI International
  • Broad Institute
  • University of California, Los Angeles
  • Harvard University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology
Original languageEnglish
Article number3344
JournalNature Communications
Issue number1
Publication statusPublished - 2020
Publication categoryResearch