Evidence map›Paper›PMID 42120360›Full record

ArticleCell death & disease2026

MCL1 inhibition to enhance the efficacy of MYB targeting in pediatric acute myeloid leukemia.

Alexia Tsakaneli, Noelia Che, Clemence Virely, Bryony McCord, Luca Gasparoli, Aerin Loe, Kent Fung, Olivia Ciampa, Nuriye Meryem Alver, Qingyin Li and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

14 authors.

Alexia Tsakaneli *Cancer Section, Developmental Biology and Cancer Department, UCL Great Ormond Street Institute of Child Health, London, UK.
Noelia Che *Cancer Section, Developmental Biology and Cancer Department, UCL Great Ormond Street Institute of Child Health, London, UK.
Clemence VirelyCancer Section, Developmental Biology and Cancer Department, UCL Great Ormond Street Institute of Child Health, London, UK.
Bryony McCordCancer Section, Developmental Biology and Cancer Department, UCL Great Ormond Street Institute of Child Health, London, UK.
Luca GasparoliCancer Section, Developmental Biology and Cancer Department, UCL Great Ormond Street Institute of Child Health, London, UK.ORCID http://orcid.org/0000-0002-6146-2124
Aerin LoeCancer Section, Developmental Biology and Cancer Department, UCL Great Ormond Street Institute of Child Health, London, UK.
Kent FungCancer Section, Developmental Biology and Cancer Department, UCL Great Ormond Street Institute of Child Health, London, UK.ORCID http://orcid.org/0000-0002-5797-1268
Olivia CiampaCancer Section, Developmental Biology and Cancer Department, UCL Great Ormond Street Institute of Child Health, London, UK.
Nuriye Meryem AlverCancer Section, Developmental Biology and Cancer Department, UCL Great Ormond Street Institute of Child Health, London, UK.
Qingyin LiCancer Section, Developmental Biology and Cancer Department, UCL Great Ormond Street Institute of Child Health, London, UK.
Jack BartramDepartment of Paediatric Haematology, Great Ormond Street Hospital for Children, London, UK.
David O'ConnorDepartment of Haematology, Cancer Institute, University College London, London, UK.
Marc MansourCancer Section, Developmental Biology and Cancer Department, UCL Great Ormond Street Institute of Child Health, London, UK.
Owen WilliamsCancer Section, Developmental Biology and Cancer Department, UCL Great Ormond Street Institute of Child Health, London, UK. owen.williams@ucl.ac.uk.ORCID http://orcid.org/0000-0002-1760-6880

Funding

Cancer Research UK (CRUK) DRCPGM\100066CHILDREN with CANCER UK 17-249CHILDREN with CANCER UK 17-249 and CwC2022\100028CHILDREN with CANCER UK CwC2022\100028Great Ormond Street Hospital Charity (GOSH) V4819Leuka 2023/JGF/002RCUK | Medical Research Council (MRC) MR/S021000/1
6 · The paper itself

Abstract

Outcomes for pediatric acute myeloid leukemia (AML) have improved significantly in recent years. However, relapsed and refractory disease remains a significant problem. The chemotherapy burden experienced by these patients makes the translational development of non-genotoxic experimental therapies attractive. We previously reported that the anti-helminth drug mebendazole induces degradation of the transcription factor MYB and has potent anti-AML activity. In the present study, we use CRISPR drop-out screening to identify genes encoding the proapoptotic regulators BAK and NOXA as hits conferring resistance to mebendazole activity in AML cells. Conversely, targeting MCL1 with a BH3-mimetic significantly enhanced the anti-AML activity of mebendazole in both AML cell lines in vitro and pediatric patient-derived xenograft (PDX) AML cells ex vivo. Treatment of mice transplanted with THP-1 AML cells or aggressive infant PDX AML cells with this drug combination significantly impaired disease progression in vivo. Our data indicate that mebendazole-induced MYB degradation in combination with MCL1 targeting is a novel non-genotoxic therapeutic strategy for pediatric AML.

Indexed as

Leukemia, Myeloid, AcuteMebendazoleMyeloid Cell Leukemia Sequence 1 ProteinProto-Oncogene Proteins c-mybAnimalsApoptosisCell Line, TumorChildFemaleHumansMiceMice, SCIDXenograft Model Antitumor AssaysMCL1 protein, humanMebendazoleMYB protein, humanMyeloid Cell Leukemia Sequence 1 ProteinProto-Oncogene Proteins c-myb

Identifiers

PMID42120360
PMCPMC13338407

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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.