Evidence map›Paper›PMID 42786200›Full record

ArticleLeukemia2026

Selective dependency of CALR-mutant myeloproliferative neoplasms on TYK2 signaling.

Milena Kalmer, Chiara Wirths, Rebecca Lemanzyk, Alessia Piergentili, Mia Mönnig, Chunxiao Zhou, Bärbel Junge, Jonas Goßen, Siddharth Gupta, Laura Schulz and 13 more

Abstract read
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In one paragraph

Article in Leukemia, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

23 authors.

Milena Kalmer *Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
Chiara Wirths *Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
Rebecca Lemanzyk *Department of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
Alessia PiergentiliInstitute for Computational Biomedicine (INM-9/IAS-5) Forschungszentrum Jülich, Wilhelm-Johnen-Straße, 52428, Jülich, Germany.
Mia MönnigDepartment of Biology/Chemistry and Center for Cellular Nanoanalytics, Osnabrück University, Osnabrück, Germany.ORCID http://orcid.org/0009-0006-6426-3661
Chunxiao ZhouDepartment of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
Bärbel JungeDepartment of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
Jonas GoßenInstitute for Computational Biomedicine (INM-9/IAS-5) Forschungszentrum Jülich, Wilhelm-Johnen-Straße, 52428, Jülich, Germany.
Siddharth GuptaDepartment of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
Laura SchulzDepartment of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.ORCID http://orcid.org/0000-0001-6525-021X
Anna SpitzerDepartment of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
Stefan TillmannDepartment of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
Kim KricheldorfDepartment of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
Joelle SchifflersDepartment of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
Kristina PannenDepartment of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
Angela GalaunerDepartment of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.
Jacob PiehlerDepartment of Biology/Chemistry and Center for Cellular Nanoanalytics, Osnabrück University, Osnabrück, Germany.
Christian PecquetLudwig Institute for Cancer Research, Brussels, Belgium.ORCID http://orcid.org/0000-0002-8623-3483
Marcelo A S de ToledoDepartment of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.ORCID http://orcid.org/0000-0003-4318-7381
Stefan N ConstantinescuSignal Transduction and Molecular Hematology Unit (SIGN), de Duve Institute, Ludwig Institute for Cancer Research, Brussels, Belgium.ORCID http://orcid.org/0000-0002-8599-2699
Giulia RossettiInstitute for Computational Biomedicine (INM-9/IAS-5) Forschungszentrum Jülich, Wilhelm-Johnen-Straße, 52428, Jülich, Germany.
Steffen KoschmiederDepartment of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany.ORCID http://orcid.org/0000-0002-1011-8171
Nicolas ChatainDepartment of Hematology, Oncology, Hemostaseology, and Stem Cell Transplantation, Faculty of Medicine, RWTH Aachen University, Pauwelsstraße 30, 52074, Aachen, Germany. nchatain@ukaachen.de.ORCID http://orcid.org/0000-0003-4485-3120

Funding

Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) NHR programBundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) NHR ProgramDeutsche Forschungsgemeinschaft (German Research Foundation) CH1509/1-1Deutsche Forschungsgemeinschaft (German Research Foundation) KO 2155/6-1Deutsche Forschungsgemeinschaft (German Research Foundation) KO 2155/7-1Deutsche Forschungsgemeinschaft (German Research Foundation) KO 2155/8-2José Carreras Leukämie-Stiftung (Deutsche José Carreras Leukämie-Stiftung) DJCLS R 16/2017RWTH Aachen University (Rheinisch-Westfälische Technische Hochschule Aachen) OPSF702
6 · The paper itself

Abstract

Myeloproliferative neoplasms (MPN) are driven by the oncoproteins JAK2V617F, mutant calreticulin (CALR), and mutant thrombopoietin receptor (TPOR; MPL), all of which activate JAK/STAT signaling. While JAK2 signaling is engaged in all MPNs, TYK2 is dispensable for JAK2V617F-driven disease. Here, we hypothesized a distinct role for TYK2 in CALR-mutant driven MPN. We found constitutive TYK2 phosphorylation in CALRdel52/ins5- and MPLW515K- but not JAK2V617F-expressing cells. Structural modeling predicted similar TPOR-binding affinities for JAK2 and TYK2, while micropatterning experiments demonstrated that both JAK2WT and JAK2V617F displace TYK2 from the receptor. The TYK2 inhibitor deucravacitinib reduced viability and STAT3/5 phosphorylation in CALRdel52/ins5- and MPLW515K- but not JAK2V617F-mutant cells, with enhanced efficacy when combined with the JAK2-selective inhibitor fedratinib. Cellular response correlated with JAK2 protein abundance, as CALRins5 JAK2

Identifiers

PMID42786200

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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.