Evidence map›Paper›PMID 40223119›Full record

ArticleCell & bioscience2025

The RBM39 degrader indisulam inhibits acute megakaryoblastic leukemia by altering the alternative splicing of ZMYND8.

Ying Yang, Zhiheng Li, Yang Yang, Peifang Xiao, Zhixu He, Zimu Zhang, Yizhen Li, Lei Shi, Xiaodong Wang, Yanfang Tao and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell & bioscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
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

30 authors.

Ying Yang *Department of Pediatrics, Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Guiyang, 550001, China.
Zhiheng Li *Institute of Pediatric Research, Children's Hospital of Soochow University, No. 92 Zhongnan Street, SIP, Suzhou, 215003, China.
Yang Yang *Institute of Pediatric Research, Children's Hospital of Soochow University, No. 92 Zhongnan Street, SIP, Suzhou, 215003, China.
Peifang Xiao *Department of Hematology, Children's Hospital of Soochow University, No. 92 Zhongnan Street, SIP, Suzhou, 215003, China.
Zhixu HeDepartment of Pediatrics, Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Guiyang, 550001, China.
Zimu ZhangInstitute of Pediatric Research, Children's Hospital of Soochow University, No. 92 Zhongnan Street, SIP, Suzhou, 215003, China.
Yizhen LiDepartment of Hematology, Children's Hospital of Soochow University, No. 92 Zhongnan Street, SIP, Suzhou, 215003, China.
Lei ShiDepartment of Medicinal Chemistry, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China.
Xiaodong WangDepartment of Orthopaedics, Children's Hospital of Soochow University, Suzhou, 215003, China.
Yanfang TaoInstitute of Pediatric Research, Children's Hospital of Soochow University, No. 92 Zhongnan Street, SIP, Suzhou, 215003, China.
Junjie FanDepartment of Hematology, Children's Hospital of Soochow University, No. 92 Zhongnan Street, SIP, Suzhou, 215003, China.
Fenli ZhangDepartment of Pediatrics, Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Guiyang, 550001, China.
Chunxia YangDepartment of Pediatrics, Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Guiyang, 550001, China.
Fahua YaoDepartment of Pediatrics, Guizhou Hospital, Shanghai Children's Medical Center, Guiyang, 550004, China.
Tongting JiChildren's Hospital of Soochow University, Suzhou, 215003, China.
Yongping ZhangDepartment of Hematology, Children's Hospital of Soochow University, No. 92 Zhongnan Street, SIP, Suzhou, 215003, China.
Bi ZhouChildren's Hospital of Soochow University, Suzhou, 215003, China.
Juanjuan YuChildren's Hospital of Soochow University, Suzhou, 215003, China.
Ailian GuoDepartment of Hematology, Children's Hospital of Soochow University, No. 92 Zhongnan Street, SIP, Suzhou, 215003, China.
Zhongling WeiDepartment of Hematology, Children's Hospital of Soochow University, No. 92 Zhongnan Street, SIP, Suzhou, 215003, China.
Wanyan JiaoChildren's Hospital of Soochow University, Suzhou, 215003, China.
Yumeng WuChildren's Hospital of Soochow University, Suzhou, 215003, China.
Yan LiChildren's Hospital of Soochow University, Suzhou, 215003, China.
Di WuInstitute of Pediatric Research, Children's Hospital of Soochow University, No. 92 Zhongnan Street, SIP, Suzhou, 215003, China.
Yijun WuChildren's Hospital of Soochow University, Suzhou, 215003, China.
Li GaoDepartment of Hematology, Children's Hospital of Soochow University, No. 92 Zhongnan Street, SIP, Suzhou, 215003, China.
Yixin HuDepartment of Hematology, Children's Hospital of Soochow University, No. 92 Zhongnan Street, SIP, Suzhou, 215003, China.
Jian PanInstitute of Pediatric Research, Children's Hospital of Soochow University, No. 92 Zhongnan Street, SIP, Suzhou, 215003, China. panjian2008@163.com.ORCID http://orcid.org/0000-0002-0292-5141
Shaoyan HuDepartment of Hematology, Children's Hospital of Soochow University, No. 92 Zhongnan Street, SIP, Suzhou, 215003, China. hsy139@126.com.
Xiaoyan YangDepartment of Pediatrics, Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Guiyang, 550001, China. 469389553@qq.com.

Funding

Key R&D Program of Jiangsu Province (Social Development) BE2022732National Natural Science Foundation 32270848National Natural Science Foundation 82060033National Natural Science Foundation 82203442National Natural Science Foundation U23A20498
6 · The paper itself

Abstract

backgroundAcute megakaryoblastic leukemia (AMKL) is a rare hematological malignancy in adults but children. Alternative splicing (AS) has been shown to affect hematological cancer progression, making splicing factors promising targets. Our research aims to investigate the efficacy of the molecular glue degrader indisulam, which targets the splicing factor RNA binding motif protein 39 (RBM39) in AMKL models.

resultsPublic drug sensitivity data analysis revealed that AMKL cell lines exhibited the highest sensitivity to indisulam compared with other tumor types. Then we confirmed that RBM39 depletion by indisulam treatment induced AMKL cell cycle arrest and apoptosis. In AMKL mouse model, indisulam treatment significantly reduced the leukemic burden and prolonged the lifetime of AMKL mice. Mechanically, integration of transcriptomic and proteomic analyses revealed that indisulam-mediated RBM39 degradation resulted in AS of the transcription factor zinc finger MYND-type containing 8 (ZMYND8), an AMKL cell growth regulator. Finally, the effectiveness of indisulam depended on DDB1- and Cul4- Associated Factor 15 (DCAF15) expression because knockout of DCAF15 rescued the indisulam-induced RBM39 degradation and mis-splicing of ZMYND8.

conclusionIndisulam is a promising therapeutic candidate for AMKL and the RBM39-mediated ZMYND8 splicing plays an important role in promoting the development of AMKL.

Indexed as

Acute megakaryoblastic leukemiaAlternative splicingIndisulamRBM39ZMYND8

Identifiers

PMID40223119
PMCPMC11995665

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