Evidence map›Paper›PMID 40188268›Full record

ArticleScientific reports2025

Inflammatory signaling pathways play a role in SYK inhibitor resistant AML.

Sarah Tausch, Christina Villinger, Gabriela Alexe, Daniel J Urban, Min Shen, Dominique Jahn, Jonas Vischedyk, Sebastian Scheich, Hubert Serve, Matthew D Hall and 3 more

Abstract read
In one paragraph

Article in Scientific reports, 2025. 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. Article
  2. Article
  3. Article
  4. 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

13 authors.

Sarah TauschDepartment of Medicine, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern Kai 7, 60594, Frankfurt am Main, Germany.
Christina VillingerDepartment of Medicine, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern Kai 7, 60594, Frankfurt am Main, Germany.
Gabriela AlexeDepartment of Pediatric Oncology, Harvard Medical School, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA, USA.
Daniel J UrbanDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Min ShenDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Dominique JahnDepartment of Medicine, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern Kai 7, 60594, Frankfurt am Main, Germany.
Jonas VischedykDepartment of Medicine, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern Kai 7, 60594, Frankfurt am Main, Germany.
Sebastian ScheichDepartment of Medicine, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern Kai 7, 60594, Frankfurt am Main, Germany.
Hubert ServeDepartment of Medicine, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern Kai 7, 60594, Frankfurt am Main, Germany.
Matthew D HallDivision of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA.
Kimberly StegmaierDepartment of Pediatric Oncology, Harvard Medical School, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA, USA.
Thomas OellerichDepartment of Medicine, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern Kai 7, 60594, Frankfurt am Main, Germany.
Anjali CremerDepartment of Medicine, Hematology/Oncology, University Hospital Frankfurt, Goethe University, Theodor-Stern Kai 7, 60594, Frankfurt am Main, Germany. a.cremer@med.uni-frankfurt.de.

Funding

Targeting Pediatric Cancer VulnerabilitiesR35CA283977 · NCI · DANA-FARBER CANCER INST · PI Kimberly Stegmaier · 2023 to 2026
$4.2M
NCI NIH HHS R35 CA283977
6 · The paper itself

Abstract

Trials have shown promising clinical activity of the selective SYK inhibitor entospletinib in patients with high expressing HOXA9/MEIS1 acute leukemias. As the development of resistance mechanisms is a common problem in the use of targeted drugs, we performed a chemical library screen to identify drug sensitivities in SYK inhibitor resistant AML cells. We identified that SYK inhibitor resistant cells displayed an increased sensitivity to glucocorticoids. Glucocorticoids are potent immunosuppressants which work in part by inhibiting the transcription of cytokine genes. RNA sequencing of entospletinib resistant cells revealed a strong enrichment of inflammatory response and TNFα signaling via NF-κB gene sets in comparison to naive cells. Naive AML cells treated with entospletinib showed a strong downregulation of the same gene sets which were upregulated in the resistant state. Our data suggest that inflammatory signaling pathways play a role in entospletinib resistant AML cells.

Indexed as

Drug Resistance, NeoplasmInflammationLeukemia, Myeloid, AcuteProtein Kinase InhibitorsSignal TransductionSyk KinaseCell Line, TumorHumansNF-kappa BNF-kappa BProtein Kinase InhibitorsSyk KinaseSYK protein, humanAcute myeloid leukemia cellsGlucocorticoidsInflammatory pathwaysResistance

Identifiers

PMID40188268
PMCPMC11972322

What OpenQuestion holds

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LicenceCC BY
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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.