Evidence map›Paper›PMID 40069287›Full record

ArticleLeukemia2025

Loss of Socs2 improves molecular responses to IFNα in a mouse model of myeloproliferative neoplasms driven by JAK2-V617F.

Marc Usart, Quentin Kimmerlin, Jan Stetka, Cédric Stoll, Shivam Rai, Tiago Almeida Fonseca, Riikka Karjalainen, Hui Hao-Shen, Julien Roux, Athimed El Taher and 4 more

Abstract read
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In one paragraph

Article in Leukemia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–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

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
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

14 authors.

Marc UsartDepartment of Biomedicine, Experimental Hematology, University Hospital Basel and University of Basel, Basel, Switzerland.
Quentin KimmerlinDepartment of Biomedicine, Experimental Hematology, University Hospital Basel and University of Basel, Basel, Switzerland.ORCID 0000-0002-1999-782X
Jan StetkaDepartment of Biomedicine, Experimental Hematology, University Hospital Basel and University of Basel, Basel, Switzerland.
Cédric StollDepartment of Biomedicine, Experimental Hematology, University Hospital Basel and University of Basel, Basel, Switzerland.
Shivam RaiDepartment of Biomedicine, Experimental Hematology, University Hospital Basel and University of Basel, Basel, Switzerland.
Tiago Almeida FonsecaDepartment of Biomedicine, Experimental Hematology, University Hospital Basel and University of Basel, Basel, Switzerland.
Riikka KarjalainenDepartment of Biomedicine, Experimental Hematology, University Hospital Basel and University of Basel, Basel, Switzerland.
Hui Hao-ShenDepartment of Biomedicine, Experimental Hematology, University Hospital Basel and University of Basel, Basel, Switzerland.
Julien RouxDepartment of Biomedicine, Bioinformatics, University of Basel and University Hospital Basel, Basel, Switzerland.ORCID 0000-0002-4192-5099
Athimed El TaherDepartment of Biomedicine, Bioinformatics, University of Basel and University Hospital Basel, Basel, Switzerland.
Dylan LynchCentre for Targeted Protein Degradation, School of Life Sciences, University of Dundee; 1 James Lindsay Place, Dundee, DD1 5JJ, UK.ORCID 0000-0001-6245-9704
Nikolai MakukhinCentre for Targeted Protein Degradation, School of Life Sciences, University of Dundee; 1 James Lindsay Place, Dundee, DD1 5JJ, UK.
Alessio CiulliCentre for Targeted Protein Degradation, School of Life Sciences, University of Dundee; 1 James Lindsay Place, Dundee, DD1 5JJ, UK.ORCID 0000-0002-8654-1670
Radek C SkodaDepartment of Biomedicine, Experimental Hematology, University Hospital Basel and University of Basel, Basel, Switzerland. radek.skoda@bcm.edu.ORCID 0000-0002-3626-9496

Funding

Cancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas) RR240024Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) 310030_185297/1Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) 310030_185297/2Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) 31003A_166613
6 · The paper itself

Abstract

Therapy with pegylated interferon alpha (pegIFNα) can induce a deep molecular response in a subset of patients with myeloproliferative neoplasms (MPN). Here we investigated the role of Socs2, a negative regulator of cytokine signaling, in modulating the response to pegIFNα in a JAK2-V617F mouse model of MPN. Deleting Socs2 in JAK2-V617F mice resulted in increased sensitivity to cytokines, without causing significant alterations in the MPN phenotype. When subjected to pegIFNα, the loss of Socs2 enhanced the depletion of JAK2-mutant hematopoietic stem cells (HSCs), evidenced by reduced chimerism in peripheral blood and bone marrow compared to vehicle controls. Additionally, pegIFNα-treated Socs2-deficient JAK2-mutant HSCs exhibited functional impairments in secondary transplantations, reflecting long-term detrimental decline of their stemness. These findings demonstrate that loss of Socs2 enhances the effectiveness of pegIFNα in depleting the JAK2-mutant HSC clone. In line with the genetic ablation of Socs2, the SOCS2 inhibitor MN714 combined with IFNα exhibited better efficacy than IFNα alone in reducing the output of CD34+ cells from PV patients in vitro. Targeting SOCS2 could therefore improve therapeutic responsiveness in MPN patients receiving interferon therapy.

Indexed as

Interferon-alphaJanus Kinase 2MutationMyeloproliferative DisordersSuppressor of Cytokine Signaling ProteinsAnimalsDisease Models, AnimalHematopoietic Stem CellsHumansMiceMice, Inbred C57BLPolyethylene GlycolsInterferon-alphaJak2 protein, mouseJanus Kinase 2Polyethylene GlycolsSocs2 protein, mouseSuppressor of Cytokine Signaling Proteins

Identifiers

PMID40069287

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.