Evidence map›Paper›PMID 32620751›Full record

ArticleNature communications2020

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

M C Wilkes, K Siva, J Chen, G Varetti, M Y Youn, H Chae, F Ek, R Olsson, T Lundbäck, D P Dever and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Diamond-Blackfan anemia.Hematology. American Society of Hematology. Education Program · 2021
    Article
  12. Review
  13. Article
  14. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors.

M C WilkesDivision of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA, 94305, USA.ORCID http://orcid.org/0000-0002-9600-6831
K SivaDepartment of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, Lund, 22184, Sweden.ORCID http://orcid.org/0000-0001-9480-4496
J ChenDepartment of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, Lund, 22184, Sweden.ORCID http://orcid.org/0000-0001-8516-0975
G VarettiInstitute for Research in Biomedicine (IRB Barcelona), Barcelona, 08028, Spain.
M Y YounDivision of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA, 94305, USA.ORCID http://orcid.org/0000-0002-8112-2346
H ChaeDivision of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA, 94305, USA.
F EkChemical Biology and Therapeutics Group, Department of Medical Science, Lund University, Lund, 22184, Sweden.ORCID http://orcid.org/0000-0002-5651-8445
R OlssonChemical Biology and Therapeutics Group, Department of Medical Science, Lund University, Lund, 22184, Sweden.ORCID http://orcid.org/0000-0002-7107-3472
T LundbäckChemical Biology Consortium Sweden (CBCS), Science for Life Laboratory, Department for Medical Biochemistry and Biophysics, Karolinska Institutet, 17177, Stockholm, Sweden.
D P DeverDepartment of Pediatrics, Stanford University, Stanford, CA, 94305, USA.ORCID http://orcid.org/0000-0001-5966-4803
T NishimuraDepartment of Genetics, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID http://orcid.org/0000-0002-5425-1708
A NarlaDivision of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA, 94305, USA.
B GladerDivision of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA, 94305, USA.ORCID http://orcid.org/0000-0003-2092-6276
H NakauchiDepartment of Genetics, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA.ORCID http://orcid.org/0000-0002-9841-6973
M H PorteusDepartment of Pediatrics, Stanford University, Stanford, CA, 94305, USA.ORCID http://orcid.org/0000-0002-3850-4648
C E RepellinBiosciences Division, SRI International, Menlo Park, CA, 94025, USA.ORCID http://orcid.org/0000-0002-6552-3318
H T GazdaBroad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
S LinDepartment of Molecular, Cell and Development Biology, University of California, Los Angeles, CA, 90095, USA.
M SerranoInstitute for Research in Biomedicine (IRB Barcelona), Barcelona, 08028, Spain.ORCID http://orcid.org/0000-0001-7177-9312
J FlygareDepartment of Molecular Medicine and Gene Therapy, Lund Stem Cell Center, Lund University, Lund, 22184, Sweden.ORCID http://orcid.org/0000-0002-1962-5276
K M SakamotoDivision of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA, 94305, USA. kmsakamo@stanford.edu.

Funding

Training in Pediatric Nonmalignant Hematology and Stem Cell BiologyT32DK098132 · NIDDK · STANFORD UNIVERSITY · PI SAKAMOTO, KATHLEEN M · 2014 to 2022
$1.9M
Signaling Pathways in MDSR01DK107286 · NIDDK · STANFORD UNIVERSITY · PI SAKAMOTO, KATHLEEN M · 2016 to 2019
$1.4M
NIDDK NIH HHS R01 DK107286NIDDK NIH HHS T32 DK098132
6 · The paper itself

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.

Indexed as

Anemia, Diamond-BlackfanAnimalsBenzamidesCell DifferentiationCell ProliferationCells, CulturedDioxolesDisease Models, AnimalErythropoiesisHematopoietic Stem CellsHumansMiceMice, TransgenicMutationPrimary Cell CultureProtein Kinase Inhibitors4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideBenzamidesDioxolesLY-2157299NLK protein, humanNlk protein, mouseProtein Kinase InhibitorsProtein Serine-Threonine KinasesPyrazolesQuinolinesRibosomal ProteinsRNA, Small InterferingRps19 protein, mouse

Identifiers

PMID32620751
PMCPMC7334220

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.