Evidence map›Paper›PMID 40755307›Full record

ArticleBritish journal of haematology2025

Synergistic potential of CDK4/6 inhibitors and ATRA in non-APL AML.

Rafał Skopek, Setenay Gupse Özcan, Paulina Chmiel, Stephanie Morgner, Jacqueline Schütt, Faezeh Ghazvini Zadegan, Clara Stanko, Małgorzata Palusińska, Karolina Maślińska-Gromadka, Yordan Sbirkov and 6 more

Abstract read
In one paragraph

Article in British journal of haematology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. 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

16 authors.

Rafał SkopekDepartment of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Magdalenka, Poland.
Setenay Gupse ÖzcanDepartment of Hematology/Oncology, Clinic of Internal Medicine II, Jena University Hospital, Jena, Germany.ORCID https://orcid.org/0009-0003-3169-6880
Paulina ChmielDepartment of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland.
Stephanie MorgnerDepartment of Hematology/Oncology, Clinic of Internal Medicine II, Jena University Hospital, Jena, Germany.
Jacqueline SchüttDepartment of Internal Medicine C, University Medicine Greifswald, Greifswald, Germany.
Faezeh Ghazvini ZadeganDepartment of Hematology/Oncology, Clinic of Internal Medicine II, Jena University Hospital, Jena, Germany.
Clara StankoDepartment of Hematology/Oncology, Clinic of Internal Medicine II, Jena University Hospital, Jena, Germany.
Małgorzata PalusińskaDepartment of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Magdalenka, Poland.
Karolina Maślińska-GromadkaDepartment of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Magdalenka, Poland.
Yordan SbirkovMedical University of Plovdiv, Plovdiv, Bulgaria.
Sven StengelDepartment of Neuropediatrics, Jena University Hospital, Jena, Germany.
Martin FischerComputational Biology Group, Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Jena, Germany.
Annamaria BrioliDepartment of Internal Medicine C, University Medicine Greifswald, Greifswald, Germany.
Arthur ZelentDepartment of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Magdalenka, Poland.
Łukasz SzymańskiDepartment of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Magdalenka, Poland.ORCID https://orcid.org/0000-0003-0148-541X
Tino SchenkDepartment of Hematology/Oncology, Clinic of Internal Medicine II, Jena University Hospital, Jena, Germany.ORCID https://orcid.org/0000-0003-3430-5876

Funding

Carl-Zeiss-StiftungDeutsche Forschungsgemeinschaft SCHE1909/2-3Narodowe Centrum Nauki 2019/33/B/NZ5/02399Narodowe Centrum Nauki 2021/41/B/NZ5/04397Thüringer Ministerium für Bildung, Wissenschaft und Kultur
6 · The paper itself

Abstract

Acute myeloid leukaemia (AML) is a heterogeneous disease characterized by diverse genetic abnormalities. The standard of care remains to be chemotherapy and stem cell transplantation. In acute promyelocytic leukaemia (APL), differentiation therapy with all-trans retinoic acid (ATRA) has significantly improved outcomes. Despite this, the success of ATRA has yet to be transferred to non-APL AML. Exploring combinations to enhance the efficacy of ATRA in non-APL AML remains a key focus. To investigate the therapeutic effect of ATRA in combination with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in non-APL AML. Non-APL AML cell lines and primary patient samples were treated with ATRA and CDK4/6 inhibitors. Key outcomes included differentiation, proliferation, cell viability and colony-forming capacity. Combination synergy was evaluated, and gene expression analysis identified pathways associated with therapeutic effects. The combination demonstrated dose-dependent effects, enhancing differentiation and reducing proliferation, cell viability and colony-forming capacity. A synergistic effect was observed across AML cell lines. Gene expression profiling revealed the co-regulation of differentiation-associated genes, unveiling the mechanisms driving therapeutic synergy. Combination of CDK4/6 inhibitors with ATRA shows potential for differentiation-based AML treatment. This approach offers a promising avenue for improved outcomes in non-APL AML.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Leukemia, Myeloid, AcuteProtein Kinase InhibitorsTretinoinCell DifferentiationCell Line, TumorCell ProliferationCell SurvivalDrug SynergismHumansCDK4 protein, humanCDK6 protein, humanCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Protein Kinase InhibitorsTretinoinacute myeloid leukaemiaAMLATRACDK4/6CDK4inon‐APLpalbociclibryuvidinesynergy

Identifiers

PMID40755307
PMCPMC12512083

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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.