Evidence map›Paper›PMID 39619245›Full record

ArticleHemaSphere2024

Dual specific STAT3/5 degraders effectively block acute myeloid leukemia and natural killer/T cell lymphoma.

Daniel Pölöske, Helena Sorger, Anna Schönbichler, Elvin D de Araujo, Heidi A Neubauer, Anna Orlova, Sanna H Timonen, Diaaeldin I Abdallah, Aleksandr Ianevski, Heikki Kuusanmäki and 21 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in HemaSphere, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. 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

31 authors.

Daniel PölöskeUnit of Functional Cancer Genomics, Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna Austria.ORCID https://orcid.org/0009-0008-0515-1728
Helena SorgerUnit of Functional Cancer Genomics, Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna Austria.
Anna SchönbichlerUnit of Functional Cancer Genomics, Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna Austria.
Elvin D de AraujoDepartment of Chemical and Physical Sciences University of Toronto Mississauga Mississauga Ontario Canada.
Heidi A NeubauerUnit of Functional Cancer Genomics, Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna Austria.
Anna OrlovaUnit of Functional Cancer Genomics, Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna Austria.
Sanna H TimonenHematology Research Unit Helsinki University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center Helsinki Finland.
Diaaeldin I AbdallahDepartment of Chemical and Physical Sciences University of Toronto Mississauga Mississauga Ontario Canada.
Aleksandr IanevskiInstitute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki Helsinki Finland.
Heikki KuusanmäkiInstitute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki Helsinki Finland.
Marta SurbekUnit of Functional Cancer Genomics, Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna Austria.
Elisabeth HeyesInstitute of Medical Biochemistry, University of Veterinary Medicine Vienna Austria.
Thomas EderInstitute of Medical Biochemistry, University of Veterinary Medicine Vienna Austria.
Christina WagnerUnit of Functional Cancer Genomics, Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna Austria.
Tobias SuskeUnit of Functional Cancer Genomics, Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna Austria.
Martin L MetzelderDepartment of Pediatric and Adolescent Surgery, Vienna General Hospital Medical University of Vienna Vienna Austria.
Michael BergmannDepartment of General Surgery, Vienna General Hospital Medical University of Vienna Vienna Austria.
Maik DahlhoffInstitute of In-Vivo and In-Vitro Models, University of Veterinary Medicine Vienna Austria.
Florian GrebienInstitute of Medical Biochemistry, University of Veterinary Medicine Vienna Austria.
Roman FleckJanpix, a Centessa Company London UK.
Christine PirkerCenter for Cancer Research, Medical University of Vienna Vienna Austria.
Walter BergerCenter for Cancer Research, Medical University of Vienna Vienna Austria.
Emir HadzijusufovicDepartment of Medicine I, Division of Hematology and Hemostaseology, Vienna General Hospital Medical University of Vienna Vienna Austria.
Wolfgang R SperrDepartment of Medicine I, Division of Hematology and Hemostaseology, Vienna General Hospital Medical University of Vienna Vienna Austria.
Lukas KennerDepartment of Pathology, Vienna General Hospital Medical University of Vienna Vienna Austria.
Peter ValentDepartment of Medicine I, Division of Hematology and Hemostaseology, Vienna General Hospital Medical University of Vienna Vienna Austria.
Tero AittokallioInstitute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki Helsinki Finland.
Marco HerlingDepartment of Medicine I, CIO-ABCD CECAD and CMMC Cologne University Cologne Germany.
Satu MustjokiHematology Research Unit Helsinki University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center Helsinki Finland.
Patrick T GunningDepartment of Chemical and Physical Sciences University of Toronto Mississauga Mississauga Ontario Canada.
Richard MorigglUnit of Functional Cancer Genomics, Institute of Animal Breeding and Genetics, University of Veterinary Medicine Vienna Austria.

Funding

Austrian Science Fund FWF I 4218
6 · The paper itself

Abstract

The transcription factors STAT3, STAT5A, and STAT5B steer hematopoiesis and immunity, but their enhanced expression and activation promote acute myeloid leukemia (AML) or natural killer/T cell lymphoma (NKCL). Current therapeutic strategies focus on blocking upstream tyrosine kinases to inhibit STAT3/5, but these kinase blockers are not selective against STAT3/5 activation and frequent resistance causes relapse, emphasizing the need for targeted drugs. We evaluated the efficacy of JPX-0700 and JPX-0750 as dual STAT3/5 binding inhibitors promoting protein degradation. JPX-0700/-0750 decreased the mRNA and protein levels of STAT3/5 targets involved in cancer survival, metabolism, and cell cycle progression, exhibiting nanomolar to low micromolar efficacy. They induced cell death and growth arrest in both AML/NKCL cell lines and primary AML patient blasts. We found that both AML/NKCL cells hijack STAT3/5 signaling through either upstream activating mutations in kinases, activating mutations in STAT3, mutational loss of negative STAT regulators, or genetic gains in anti-apoptotic, pro-proliferative, or epigenetic-modifying STAT3/5 targets. This emphasizes a vicious cycle for proliferation and survival through STAT3/5. Both JPX-0700/-0750 treatment reduced leukemic cell growth in human AML or NKCL xenograft mouse models significantly, being well tolerated by mice. Synergistic cell death was induced upon combinatorial use with approved chemotherapeutics in AML/NKCL cells.

Identifiers

PMID39619245
PMCPMC11603092

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.