Evidence map›Paper›PMID 38216972›Full record

ArticleGenome biology2024

RNA-binding protein RBM5 plays an essential role in acute myeloid leukemia by activating the oncogenic protein HOXA9.

Mengli Zhang, Judith Hyle, Xiaowen Chen, Ye Xin, Yingcai Jin, Jianxiang Zhang, Xue Yang, Xinfeng Chen, Shaela Wright, Zhenling Liu and 9 more

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

13 citing papers in PubMed, 7 citations in OpenAlex.

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  11. Prospective Analysis of Mesotheliomas in Subjects With BAP1 Cancer Syndrome: Clinical Characteristics and Epigenetic Correlates of Disease.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2025
    Observational
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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

19 authors at 3 institutions in 2 countries.

Mengli ZhangCyrus Tang Medical Institute, National Clinical Research Center for Hematologic Diseases, State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215123, Jiangsu, China.
Judith HyleDepartment of Tumor Cell Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA.
Xiaowen ChenDivision of Hematology and Oncology, Shenzhen Children's Hospital, Shenzhen Institute of Pediatrics, 7019 Yi Tian Road, Shenzhen, 518038, China.
Ye XinCyrus Tang Medical Institute, National Clinical Research Center for Hematologic Diseases, State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215123, Jiangsu, China.
Yingcai JinCyrus Tang Medical Institute, National Clinical Research Center for Hematologic Diseases, State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215123, Jiangsu, China.
Jianxiang ZhangCyrus Tang Medical Institute, National Clinical Research Center for Hematologic Diseases, State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215123, Jiangsu, China.
Xue YangCyrus Tang Medical Institute, National Clinical Research Center for Hematologic Diseases, State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215123, Jiangsu, China.
Xinfeng ChenCyrus Tang Medical Institute, National Clinical Research Center for Hematologic Diseases, State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215123, Jiangsu, China.
Shaela WrightDepartment of Tumor Cell Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA.
Zhenling LiuDepartment of Tumor Cell Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA.
Wojciech RosikiewiczCenter for Applied Bioinformatics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA.
Beisi XuCenter for Applied Bioinformatics, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA.
Liusheng HeCore Facility of Flow Cytometry, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA.
Hong LiuNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, 215123, Jiangsu, China.
Nana PingNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, 215123, Jiangsu, China.
Depei WuNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, 215123, Jiangsu, China.
Feiqiu WenDivision of Hematology and Oncology, Shenzhen Children's Hospital, Shenzhen Institute of Pediatrics, 7019 Yi Tian Road, Shenzhen, 518038, China.
Chunliang LiDepartment of Tumor Cell Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA. chunliang.li@stjude.org.ORCID 0000-0002-5938-5510
Peng XuCyrus Tang Medical Institute, National Clinical Research Center for Hematologic Diseases, State Key Laboratory of Radiation Medicine and Protection, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, 215123, Jiangsu, China. pengxu@suda.edu.cn.
Soochow University · CNSt. Jude Children's Research Hospital · USShenzhen Children's Hospital · CN

Funding

Key Technologies Research and Development Program 2022YFC25022701Key Technologies Research and Development Program 2022YFC2502700Key Technologies Research and Development Program 2022YFC2502702National Natural Science Foundation of China 82170119Science and Technology Support Program of Jiangsu Province BK20210714Science and Technology Support Program of Jiangsu Province JSSCBS20210692Suzhou Gusu Medical Youth Talent ZXL2022443
6 · The paper itself

Abstract

backgroundThe oncogenic protein HOXA9 plays a critical role in leukemia transformation and maintenance, and its aberrant expression is a hallmark of most aggressive acute leukemia. Although inhibiting the upstream regulators of HOXA9 has been proven as a significant therapeutic intervention, the comprehensive regulation network controlling HOXA9 expression in leukemia has not been systematically investigated.

resultsHere, we perform genome-wide CRISPR/Cas9 screening in the HOXA9-driven reporter acute leukemia cells. We identify a poorly characterized RNA-binding protein, RBM5, as the top candidate gene required to maintain leukemia cell fitness. RBM5 is highly overexpressed in acute myeloid leukemia (AML) patients compared to healthy individuals. RBM5 loss triggered by CRISPR knockout and shRNA knockdown significantly impairs leukemia maintenance in vitro and in vivo. Through domain CRISPR screening, we reveal that RBM5 functions through a noncanonical transcriptional regulation circuitry rather than RNA splicing, such an effect depending on DNA-binding domains. By integrative analysis and functional assays, we identify HOXA9 as the downstream target of RBM5. Ectopic expression of HOXA9 rescues impaired leukemia cell proliferation upon RBM5 loss. Importantly, acute protein degradation of RBM5 through auxin-inducible degron system immediately reduces HOXA9 transcription.

conclusionsWe identify RBM5 as a new upstream regulator of HOXA9 and reveal its essential role in controlling the survival of AML. These functional and molecular mechanisms further support RBM5 as a promising therapeutic target for myeloid leukemia treatment.

Indexed as

Homeodomain ProteinsLeukemia, Myeloid, AcuteCell Cycle ProteinsCell ProliferationDNA-Binding ProteinsHumansNeoplasm ProteinsOncogene ProteinsRNA-Binding ProteinsTumor Suppressor ProteinsCell Cycle ProteinsDNA-Binding Proteinshomeobox protein HOXA9Homeodomain ProteinsNeoplasm ProteinsOncogene ProteinsRBM5 protein, humanRNA-Binding ProteinsTumor Suppressor ProteinsAcute myeloid leukemiaCRISPR screenGenome editingHOXA9RBM5

Identifiers

PMID38216972
PMCPMC10785552
OpenAlexW4390789505

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.