Evidence map›Paper›PMID 40175625›Full record

ArticleLeukemia2025

CircTADA2A stabilizes p53 via interacting with TRIM28 and suppresses the maintenance of FLT3-ITD acute myeloid leukemia.

Ran Li, Xiaolu Wu, Kai Xue, Shishuang Wu, Ge Jiang, Mengke He, Yi Xia, Hailing Liu, Miao Zhong, Jianyong Li and 2 more

Abstract read
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In one paragraph

Article in Leukemia, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. 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

12 authors.

Ran Li *Department of Hematology, Jiangsu Province Hospital, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China.ORCID 0000-0003-1526-0182
Xiaolu Wu *Department of Child Health Care, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, China.
Kai Xue *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.
Shishuang WuShanghai 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.
Ge JiangShanghai 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.
Mengke HeShanghai 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.
Yi XiaDepartment of Hematology, Jiangsu Province Hospital, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Hailing LiuDepartment of Hematology, Jiangsu Province Hospital, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Miao ZhongDepartment of Hematology, Jiangsu Province Hospital, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Jianyong LiDepartment of Hematology, Jiangsu Province Hospital, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China. lijianyonglm@126.com.ORCID 0000-0002-9931-4055
Lei FanDepartment of Hematology, Jiangsu Province Hospital, the First Affiliated Hospital with Nanjing Medical University, Nanjing, China. fanlei@jsph.org.cn.
Junmin LiShanghai 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. lijunminhematology@163.com.ORCID 0000-0003-1338-8764

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Internal tandem duplication mutations in the FMS-like tyrosine kinase 3 (FLT3-ITDs) occur in 25%-30% of acute myeloid leukemia (AML) cases and are associated with adverse prognosis. RNA-based therapeutics exhibit significant potential for treating diseases, prompting us to develop a novel circular RNA (circRNA)-based therapeutic strategy for FLT3-ITD AML. Here, we find circTADA2A is downregulated in FLT3-ITD AML patients. We further demonstrate that the downregulation of circTADA2A is critical for the proliferation of human FLT3-ITD AML cells, the sustenance of AML, and the self-renewal of leukemia stem/initiating cells (LSCs/LICs). Mechanistically, circTADA2A inhibits the TRIM28/MDM2 complexes formation by competitively binding to TRIM28, resulting in decreased levels of p53 ubiquitination and activating the p53 pathway. Importantly, in vitro transcription of circTADA2A and in vivo delivery via lipid nanoparticles (LNPs) significantly enhance the elimination of FLT3-ITD leukemia cells in combination with quizartinib treatment. In conclusion, our work uncovers the crucial functions of circTADA2A in the maintenance of FLT3-ITD AML and highlights a translationally important circTADA2A-based therapeutic approach for FLT3-ITD AML treatment.

Indexed as

fms-Like Tyrosine Kinase 3Leukemia, Myeloid, AcuteRNA, CircularTripartite Motif-Containing Protein 28Tumor Suppressor Protein p53AnimalsCell Line, TumorCell ProliferationGene Expression Regulation, LeukemicHumansMiceMutationTandem Repeat SequencesUbiquitinationFLT3 protein, humanfms-Like Tyrosine Kinase 3RNA, CircularTP53 protein, humanTRIM28 protein, humanTripartite Motif-Containing Protein 28Tumor Suppressor Protein p53

Identifiers

PMID40175625

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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.