Evidence map›Paper›PMID 39805831›Full record

ArticleNature communications2025

Oncogenic role of RARG rearrangements in acute myeloid leukemia resembling acute promyelocytic leukemia.

Feng Wang, Luyao Zhao, Yun Tan, Xufeng Cen, Huan Gao, Huimin Jiang, Ying Liu, Yunxuan Li, Tingting Zhang, Chenxi Zhao and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. The Influences of RARγ on the Behavior of Normal and Cancer Stem Cells.International journal of molecular sciences · 2026
    Review
  5. Article
  6. 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

19 authors.

Feng Wang *State Key Laboratory of Bioactive Substance and Function of Natural Medicines, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Luyao Zhao *State Key Laboratory of Bioactive Substance and Function of Natural Medicines, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Yun Tan *Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xufeng Cen *Liangzhu Laboratory, Zhejiang University, Hangzhou, China.
Huan GaoMarine College, Shandong University, Weihai, China.
Huimin JiangState Key Laboratory of Bioactive Substance and Function of Natural Medicines, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Ying LiuState Key Laboratory of Bioactive Substance and Function of Natural Medicines, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Yunxuan LiState Key Laboratory of Bioactive Substance and Function of Natural Medicines, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Tingting ZhangState Key Laboratory of Bioactive Substance and Function of Natural Medicines, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Chenxi ZhaoState Key Laboratory of Bioactive Substance and Function of Natural Medicines, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Ting ShiDepartment of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.
Guilin XuShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Churan WangShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jiong HuShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID http://orcid.org/0000-0002-5613-1195
Xia LiMarine College, Shandong University, Weihai, China.
Ya-Zhen QinNational Clinical Research Center for Hematologic Disease, Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China. qin2000@aliyun.com.ORCID http://orcid.org/0000-0002-1548-0946
Kankan WangShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. kankanwang@shsmu.edu.cn.ORCID http://orcid.org/0000-0001-7198-2134
Hong-Hu ZhuDepartment of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China. zhuhhdoc@163.com.ORCID http://orcid.org/0000-0003-2343-0436
Ke LiState Key Laboratory of Bioactive Substance and Function of Natural Medicines, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. like1986@163.com.ORCID http://orcid.org/0000-0001-5634-6308

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82273973
6 · The paper itself

Abstract

Acute myeloid leukemia (AML) featuring retinoic acid receptor-gamma (RARG) rearrangements exhibits morphological features resembling those of acute promyelocytic leukemia but is associated with drug resistance and poor clinical outcomes. However, the mechanisms underlying the role of RARG fusions in leukemogenesis remain elusive. Here, we show that RARG fusions disrupt myeloid differentiation and promote proliferation and self-renewal of hematopoietic stem and progenitor cells (HSPCs) by upregulating BCL2 and ATF3. RARG fusions overexpression leads to preleukemic phenotypes but fails to induce oncogenic transformation. However, the co-occurrence of RARG fusions and heterozygous Wt1 loss induce fully penetrant AML by activating MYC and HOXA9/MEIS1 targets. Leveraging Connectivity Map resources and high-throughput screening, we identify venetoclax, homoharringtonine, and daunorubicin as potential therapeutic options for RARG-AML. Overall, our findings provide pivotal insights into the molecular mechanisms governed by RARG fusions and enhanced by WT1 loss in AML development and propose a rational therapeutic strategy for RARG-AML.

Indexed as

Gene RearrangementLeukemia, Myeloid, AcuteLeukemia, Promyelocytic, AcuteReceptors, Retinoic AcidAnimalsAntineoplastic AgentsBridged Bicyclo Compounds, HeterocyclicCell DifferentiationCell Line, TumorCell ProliferationDaunorubicinHematopoietic Stem CellsHomeodomain ProteinsHomoharringtonineHumansMiceAntineoplastic AgentsBridged Bicyclo Compounds, HeterocyclicDaunorubicinhomeobox protein HOXA9Homeodomain ProteinsHomoharringtonineMeis1 protein, mouseMyeloid Ecotropic Viral Integration Site 1 ProteinOncogene Proteins, FusionProto-Oncogene Proteins c-mycReceptors, Retinoic AcidRetinoic Acid Receptor gammaSulfonamidesvenetoclaxWT1 protein, humanWT1 Proteins

Identifiers

PMID39805831
PMCPMC11729897

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.