Evidence map›Paper›PMID 34638998›Full record

ArticleInternational journal of molecular sciences2021

BCL-2 Inhibitor ABT-737 Effectively Targets Leukemia-Initiating Cells with Differential Regulation of Relevant Genes Leading to Extended Survival in a NRAS/BCL-2 Mouse Model of High Risk-Myelodysplastic Syndrome.

Petra Gorombei, Fabien Guidez, Saravanan Ganesan, Mathieu Chiquet, Andrea Pellagatti, Laure Goursaud, Nilgun Tekin, Stephanie Beurlet, Satyananda Patel, Laura Guerenne and 19 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in International journal of molecular sciences, 2021. 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
1.5field-weighted citation impact, top 17% 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, 17 citations in OpenAlex.

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  11. Molecular Mechanisms and Therapies of Myeloid Leukaemia.International journal of molecular sciences · 2022
    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

29 authors at 7 institutions in 3 countries.

Petra GorombeiINSERM UMR-S1131, Université de Paris, Institut de la Recherche Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis Hôpital, 75010 Paris, France.
Fabien GuidezINSERM UMR-S1131, Université de Paris, Institut de la Recherche Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis Hôpital, 75010 Paris, France.ORCID 0000-0003-1380-4473
Saravanan GanesanINSERM UMR-S1131, Université de Paris, Institut de la Recherche Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis Hôpital, 75010 Paris, France.
Mathieu ChiquetINSERM UMR-S1131, Université de Paris, Institut de la Recherche Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis Hôpital, 75010 Paris, France.
Andrea PellagattiBlood Cancer UK Molecular Haematology Unit, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, and BRC Haematology Theme, Oxford OX3 9DU, UK.ORCID 0000-0002-6122-0221
Laure GoursaudINSERM UMR-S1131, Université de Paris, Institut de la Recherche Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis Hôpital, 75010 Paris, France.
Nilgun TekinINSERM UMR-S1131, Université de Paris, Institut de la Recherche Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis Hôpital, 75010 Paris, France.ORCID 0000-0003-3954-7495
Stephanie BeurletINSERM UMR-S1131, Université de Paris, Institut de la Recherche Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis Hôpital, 75010 Paris, France.
Satyananda PatelINSERM UMR-S1131, Université de Paris, Institut de la Recherche Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis Hôpital, 75010 Paris, France.ORCID 0000-0003-4087-1866
Laura GuerenneINSERM UMR-S1131, Université de Paris, Institut de la Recherche Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis Hôpital, 75010 Paris, France.
Carole Le PogamINSERM UMR-S1131, Université de Paris, Institut de la Recherche Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis Hôpital, 75010 Paris, France.
Niclas SetterbladImagerie Département, Université de Paris, Institut de la Recherche Saint-Louis, 75010 Paris, France.ORCID 0000-0002-1899-5435
Pierre de la GrangeGenoSplice Technology, Paris Biotech Santé, 29 Rue du Faubourg Saint-Jacques, 75014 Paris, France.ORCID 0000-0001-6361-1878
Christophe LeBoeufINSERM UMR-S942, Université de Paris, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, 75010 Paris, France.ORCID 0000-0002-6537-0550
Anne JaninINSERM UMR-S942, Université de Paris, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, 75010 Paris, France.
Maria-Elena NogueraDepartment of Cytology, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, 75010 Paris, France.
Laure Sarda-MantelRadiopharmacie AP-HP, Hôpital Saint-Louis, Service Medicine Nuclear, AP-HP Lariboisiere, 75010 Paris, France.
Pascale MerletNuclear Medicine, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, 75010 Paris, France.
Jacqueline BoultwoodBlood Cancer UK Molecular Haematology Unit, Nuffield Division of Clinical Laboratory Sciences, Radcliffe Department of Medicine, University of Oxford, and BRC Haematology Theme, Oxford OX3 9DU, UK.ORCID 0000-0002-4330-2928
Marina KonoplevaM. D. Anderson Cancer Center, The University of Texas, Houston, TX 77030, USA.
Michael AndreeffM. D. Anderson Cancer Center, The University of Texas, Houston, TX 77030, USA.ORCID 0000-0002-1144-1958
Robert WestDepartment of Public Health, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.
Marika PlaINSERM UMR-S1131, Université de Paris, Institut de la Recherche Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis Hôpital, 75010 Paris, France.
Lionel AdèsINSERM UMR-S944, Université de Paris, Institut de la Recherche Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, 75010 Paris, France.
Pierre FenauxINSERM UMR-S944, Université de Paris, Institut de la Recherche Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, 75010 Paris, France.
Patricia KriefINSERM UMR-S1131, Université de Paris, Institut de la Recherche Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis Hôpital, 75010 Paris, France.ORCID 0000-0001-5106-466X
Christine ChomienneINSERM UMR-S1131, Université de Paris, Institut de la Recherche Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis Hôpital, 75010 Paris, France.
Nader OmidvarDepartment of Haematology, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.
Rose Ann PaduaINSERM UMR-S1131, Université de Paris, Institut de la Recherche Saint-Louis, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis Hôpital, 75010 Paris, France.ORCID 0000-0001-9964-7864
Inserm · FRAssistance Publique – Hôpitaux de Paris · FRCardiff University · GBThe University of Texas MD Anderson Cancer Center · USUniversity of Oxford · GBParis Biotech Santé · FRUniversité Paris Cité · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

During transformation, myelodysplastic syndromes (MDS) are characterized by reducing apoptosis of bone marrow (BM) precursors. Mouse models of high risk (HR)-MDS and acute myelogenous leukemia (AML) post-MDS using mutant NRAS and overexpression of human BCL-2, known to be poor prognostic indicators of the human diseases, were created. We have reported the efficacy of the BCL-2 inhibitor, ABT-737, on the AML post-MDS model; here, we report that this BCL-2 inhibitor also significantly extended survival of the HR-MDS mouse model, with reductions of BM blasts and lineage negative/Sca1+/KIT+ (LSK) cells. Secondary transplants showed increased survival in treated compared to untreated mice. Unlike the AML model, BCL-2 expression and RAS activity decreased following treatment and the RAS:BCL-2 complex remained in the plasma membrane. Exon-specific gene expression profiling (GEP) of HR-MDS mice showed 1952 differentially regulated genes upon treatment, including genes important for the regulation of stem cells, differentiation, proliferation, oxidative phosphorylation, mitochondrial function, and apoptosis; relevant in human disease. Spliceosome genes, found to be abnormal in MDS patients and downregulated in our HR-MDS model, such as Rsrc1 and Wbp4, were upregulated by the treatment, as were genes involved in epigenetic regulation, such as DNMT3A and B, upregulated upon disease progression and downregulated upon treatment.

Indexed as

AnimalsApoptosisBiphenyl CompoundsBone MarrowBone Marrow CellsCell ProliferationDisease Models, AnimalGene Expression ProfilingGene Expression RegulationKaplan-Meier EstimateMiceMice, TransgenicMonomeric GTP-Binding ProteinsMyelodysplastic SyndromesNitrophenolsPiperazinesABT-737BCL2 protein, humanBiphenyl CompoundsMonomeric GTP-Binding ProteinsNitrophenolsNras protein, mousePiperazinesProto-Oncogene Proteins c-bcl-2SulfonamidesABT-737BCL-2gene regulationHR-MDS

Identifiers

PMID34638998
PMCPMC8508829
OpenAlexW3203806696

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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.