Evidence map›Paper›PMID 33667305›Full record

ArticleBlood2021

JAK2-V617F and interferon-α induce megakaryocyte-biased stem cells characterized by decreased long-term functionality.

Tata Nageswara Rao, Nils Hansen, Jan Stetka, Damien Luque Paz, Milena Kalmer, Julian Hilfiker, Max Endele, Nouraiz Ahmed, Lucia Kubovcakova, Margareta Rybarikova and 9 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
6.5field-weighted citation impact, top 2% of its field
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

43 citing papers in PubMed, 67 citations in OpenAlex.

  1. Article
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  4. Review
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  7. Review
  8. Sabotaged Integral HSC Heterogeneity Underlies Essential Thrombocythemia Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Direct megakaryopoiesis.Current opinion in hematology · 2025
    Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 6 institutions in 4 countries.

Tata Nageswara RaoDepartment of Biomedicine, Experimental Hematology, University Hospital Basel-University of Basel, Basel, Switzerland.
Nils HansenDepartment of Biomedicine, Experimental Hematology, University Hospital Basel-University of Basel, Basel, Switzerland.
Jan StetkaDepartment of Biomedicine, Experimental Hematology, University Hospital Basel-University of Basel, Basel, Switzerland.
Damien Luque PazDepartment of Biomedicine, Experimental Hematology, University Hospital Basel-University of Basel, Basel, Switzerland.
Milena KalmerDepartment of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, Rheinisch-Westfälische Technische Hochschul (RWTH) Aachen University, Aachen, Germany.
Julian HilfikerDepartment of Biomedicine, Experimental Hematology, University Hospital Basel-University of Basel, Basel, Switzerland.
Max EndeleDepartment of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zurich, Basel, Switzerland.
Nouraiz AhmedDepartment of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zurich, Basel, Switzerland.
Lucia KubovcakovaDepartment of Biomedicine, Experimental Hematology, University Hospital Basel-University of Basel, Basel, Switzerland.
Margareta RybarikovaDepartment of Biomedicine, Experimental Hematology, University Hospital Basel-University of Basel, Basel, Switzerland.
Hui Hao-ShenDepartment of Biomedicine, Experimental Hematology, University Hospital Basel-University of Basel, Basel, Switzerland.
Florian GeierDepartment of Biomedicine, Experimental Hematology, University Hospital Basel-University of Basel, Basel, Switzerland.
Christian BeiselDepartment of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zurich, Basel, Switzerland.
Stefan DirnhoferInstitute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland; and.
Timm SchroederDepartment of Biosystems Science and Engineering, Eidgenössische Technische Hochschule Zurich, Basel, Switzerland.
Tim H BrümmendorfDepartment of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, Rheinisch-Westfälische Technische Hochschul (RWTH) Aachen University, Aachen, Germany.
Dominik WolfInternal Medicine V, Department of Hematology and Oncology, Medical University Innsbruck, Innsbruck, Austria.
Steffen KoschmiederDepartment of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, Rheinisch-Westfälische Technische Hochschul (RWTH) Aachen University, Aachen, Germany.
Radek C SkodaDepartment of Biomedicine, Experimental Hematology, University Hospital Basel-University of Basel, Basel, Switzerland.
University of Basel · CHBoard of the Swiss Federal Institutes of Technology · CHRWTH Aachen University · DEInnsbruck Medical University · ATSIB Swiss Institute of Bioinformatics · CHUniversity Hospital of Basel · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We studied a subset of hematopoietic stem cells (HSCs) that are defined by elevated expression of CD41 (CD41hi) and showed bias for differentiation toward megakaryocytes (Mks). Mouse models of myeloproliferative neoplasms (MPNs) expressing JAK2-V617F (VF) displayed increased frequencies and percentages of the CD41hi vs CD41lo HSCs compared with wild-type controls. An increase in CD41hi HSCs that correlated with JAK2-V617F mutant allele burden was also found in bone marrow from patients with MPN. CD41hi HSCs produced a higher number of Mk-colonies of HSCs in single-cell cultures in vitro, but showed reduced long-term reconstitution potential compared with CD41lo HSCs in competitive transplantations in vivo. RNA expression profiling showed an upregulated cell cycle, Myc, and oxidative phosphorylation gene signatures in CD41hi HSCs, whereas CD41lo HSCs showed higher gene expression of interferon and the JAK/STAT and TNFα/NFκB signaling pathways. Higher cell cycle activity and elevated levels of reactive oxygen species were confirmed in CD41hi HSCs by flow cytometry. Expression of Epcr, a marker for quiescent HSCs inversely correlated with expression of CD41 in mice, but did not show such reciprocal expression pattern in patients with MPN. Treatment with interferon-α further increased the frequency and percentage of CD41hi HSCs and reduced the number of JAK2-V617F+ HSCs in mice and patients with MPN. The shift toward the CD41hi subset of HSCs by interferon-α provides a possible mechanism of how interferon-α preferentially targets the JAK2 mutant clone.

Indexed as

AnimalsGene Knock-In TechniquesHematopoietic Stem CellsHumansInterferon-alphaJanus Kinase 2MegakaryocytesMiceMice, TransgenicMyeloproliferative DisordersPlatelet Membrane Glycoprotein IIbPoint MutationInterferon-alphaJAK2 protein, humanJak2 protein, mouseJanus Kinase 2Platelet Membrane Glycoprotein IIb

Identifiers

PMID33667305
PMCPMC8103999
OpenAlexW3133520808

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.