Evidence map›Paper›PMID 37108344›Full record

ArticleInternational journal of molecular sciences2023

Synergistic Action of MCL-1 Inhibitor with BCL-2/BCL-XL or MAPK Pathway Inhibitors Enhances Acute Myeloid Leukemia Cell Apoptosis and Differentiation.

Małgorzata Opydo, Anna Mlyczyńska, Ewa Mlyczyńska, Agnieszka Rak, Elzbieta Kolaczkowska

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.7field-weighted citation impact, top 16% of its field
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

11 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. A Phase 1 First-in-Human Study of the MCL-1 Inhibitor AZD5991 in Patients with Relapsed/Refractory Hematologic Malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024
    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

5 authors at 1 institution in 1 country.

Małgorzata OpydoLaboratory of Experimental Hematology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, 30-387 Krakow, Poland.ORCID 0000-0002-8744-8451
Anna MlyczyńskaLaboratory of Experimental Hematology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, 30-387 Krakow, Poland.
Ewa MlyczyńskaLaboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, 30-387 Krakow, Poland.ORCID 0000-0002-7471-0553
Agnieszka RakLaboratory of Physiology and Toxicology of Reproduction, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, 30-387 Krakow, Poland.ORCID 0000-0002-9572-7151
Elzbieta KolaczkowskaLaboratory of Experimental Hematology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, 30-387 Krakow, Poland.ORCID 0000-0002-3573-3584
Jagiellonian University · PL

Funding

Polpharma Scientific Foundation for Małgorzata Opydo (2020-2023)
6 · The paper itself

Abstract

Acute myeloid leukemia (AML) is a hematological malignancy characterized by excessive proliferation of abnormal myeloid precursors accompanied by a differentiation block and inhibition of apoptosis. Increased expression of an anti-apoptotic MCL-1 protein was shown to be critical for the sustained survival and expansion of AML cells. Therefore, herein, we examined the pro-apoptotic and pro-differentiating effects of S63845, a specific inhibitor of MCL-1, in a single-agent treatment and in combination with BCL-2/BCL-XL inhibitor, ABT-737, in two AML cell lines: HL-60 and ML-1. Additionally, we determined whether inhibition of the MAPK pathway had an impact on the sensitivity of AML cells to S63845. To assess AML cells' apoptosis and differentiation, in vitro studies were performed using PrestoBlue assay, Coulter electrical impedance method, flow cytometry, light microscopy and Western blot techniques. S63845 caused a concentration-dependent decrease in the viability of HL-60 and ML-1 cells and increased the percentage of apoptotic cells. Combined treatment with S63845 and ABT-737 or MAPK pathway inhibitor enhanced apoptosis but also induced differentiation of tested cells, as well as altering the expression of the MCL-1 protein. Taken together, our data provide the rationale for further studies regarding the use of MCL-1 inhibitor in combination with other pro-survival protein inhibitors.

Indexed as

Antineoplastic AgentsLeukemia, Myeloid, AcuteApoptosisApoptosis Regulatory ProteinsBiphenyl CompoundsCell DifferentiationCell Line, TumorHumansMAP Kinase Signaling SystemMyeloid Cell Leukemia Sequence 1 ProteinNitrophenolsPiperazinesProto-Oncogene Proteins c-bcl-2PyrimidinesSulfonamidesThiophenesABT-737Antineoplastic AgentsApoptosis Regulatory ProteinsBiphenyl CompoundsMyeloid Cell Leukemia Sequence 1 ProteinNitrophenolsPiperazinesProto-Oncogene Proteins c-bcl-2PyrimidinesS63845SulfonamidesThiophenesABT-737acute myeloid leukemiaapoptosisBCL-2 inhibitorsdifferentiationMAPK signaling pathwayS63845

Identifiers

PMID37108344
PMCPMC10138770
OpenAlexW4365454043

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.