Evidence map›Paper›PMID 36567628›Full record

ArticleMolecular oncology2023

ACC010, a novel BRD4 inhibitor, synergized with homoharringtonine in acute myeloid leukemia with FLT3-ITD.

Yu Qian, Xiang Zhang, Shihui Mao, Wenwen Wei, Xiangjie Lin, Qing Ling, Wenle Ye, Fenglin Li, Jiajia Pan, Yutong Zhou and 6 more

Open access · goldAbstract read
In one paragraph

Article in Molecular oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.3field-weighted citation impact, top 43% 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

2 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. 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 at 4 institutions in 2 countries.

Yu QianDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Xiang ZhangDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Shihui MaoDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Wenwen WeiDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Xiangjie LinDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Qing LingZhejiang Provincial Key Laboratory of Hematopoietic Malignancy, Zhejiang University, Hangzhou, China.
Wenle YeDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Fenglin LiThe Affiliated People's Hospital of Ningbo University, China.
Jiajia PanDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Yutong ZhouDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Yanchun ZhaoDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Xin HuangDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Jiansong HuangDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Hongyan TongDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Jie SunDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Jie JinDepartment of Hematology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.ORCID 0000-0002-8166-9915
First Affiliated Hospital Zhejiang University · CNCluster in Biomedicine · ITNingbo University Affiliated Hospital · CNZhejiang University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bromodomain-containing protein 4 (BRD4) inhibitors have been clinically developed to treat acute myeloid leukemia (AML), but their application is limited by the possibility of drug resistance, which is reportedly associated with the activation of the WNT/β-catenin pathway. Meanwhile, homoharringtonine (HHT), a classic antileukemia drug, possibly inhibits the WNT/β-catenin pathway. In this study, we attempted to combine a novel BRD4 inhibitor (ACC010) and HHT to explore their synergistic lethal effects in treating AML. Here, we found that co-treatment with ACC010 and HHT synergistically inhibited cell proliferation, induced apoptosis, and arrested the cell cycle in FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD)-positive AML cells in vitro, and significantly inhibiting AML progression in vivo. Mechanistically, ACC010 and HHT cooperatively downregulated MYC and inhibited FLT3 activation. Further, when HHT was added, ACC010-resistant cells demonstrated a good synergy. We also extended our study to the mouse BaF3 cell line with FLT3-inhibitor-resistant FLT3-ITD/tyrosine kinase domain mutations and AML cells without FLT3-ITD. Collectively, our results suggested that the combination treatment of ACC010 and HHT might be a promising strategy for AML patients, especially those carrying FLT3-ITD.

Indexed as

beta CateninLeukemia, Myeloid, AcuteAnimalsApoptosisCell Line, Tumorfms-Like Tyrosine Kinase 3HomoharringtonineHumansMiceMutationNuclear ProteinsProtein Kinase InhibitorsTranscription Factorsbeta Cateninfms-Like Tyrosine Kinase 3HomoharringtonineNuclear ProteinsProtein Kinase InhibitorsTranscription Factorsacute myeloid leukemiaFLT3-ITDhomoharringtoninenovel BRD4 Inhibitor ACC010

Identifiers

PMID36567628
PMCPMC10323884
OpenAlexW4312194905

What OpenQuestion holds

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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.