Evidence map›Paper›PMID 41564858›Full record

ArticleCell reports. Medicine2026

Sequence-dependent splicing dysregulation drives therapy resistance in pediatric AML.

Yue Huang, Peifang Xiao, Lei Qin, Li Gao, Yang Zhao, Jingru Sui, Wenting Hu, Lei Zhou, Nan Han, Xuan Lv and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2026. 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
–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

2 citing papers in PubMed.

  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

18 authors.

Yue HuangDepartment of Computation Biology, China National Center for Bioinformation, Beijing 100101, China; Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Peifang XiaoDepartment of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou 215025, China.
Lei QinBeijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Li GaoDepartment of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou 215025, China.
Yang ZhaoDepartment of Computation Biology, China National Center for Bioinformation, Beijing 100101, China; Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
Jingru SuiDepartment of Computation Biology, China National Center for Bioinformation, Beijing 100101, China; Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Wenting HuKey Laboratory of Pediatric Hematology & Oncology of the Ministry of Health of China, Department of Hematology & Oncology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
Lei ZhouDepartment of Computation Biology, China National Center for Bioinformation, Beijing 100101, China; Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Nan HanDepartment of Computation Biology, China National Center for Bioinformation, Beijing 100101, China; Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Xuan LvDepartment of Computation Biology, China National Center for Bioinformation, Beijing 100101, China; Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Kunying ChenDepartment of Computation Biology, China National Center for Bioinformation, Beijing 100101, China; Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Yu LiuPediatric Translational Medicine Institute, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
Hanhong LinDepartment of Computation Biology, China National Center for Bioinformation, Beijing 100101, China; Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Shuhong ShenKey Laboratory of Pediatric Hematology & Oncology of the Ministry of Health of China, Department of Hematology & Oncology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
Omar Abdel-WahabMolecular Pharmacology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Shaoyan HuDepartment of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou 215025, China. Electronic address: hushaoyan@suda.edu.cn.
Zhaoqi LiuDepartment of Computation Biology, China National Center for Bioinformation, Beijing 100101, China; Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: liuzq@big.ac.cn.
Qianfei WangBeijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: wangqf@big.ac.cn.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

Despite improvements in pediatric acute myeloid leukemia (AML) prognosis, about 30% of patients relapse after initial chemotherapy and have poor survival. However, the genetic basis of resistance remains unclear for most patients. To better understand the mechanistic basis and overcome treatment resistance, we analyze RNA sequencing (RNA-seq) data from 702 pediatric AML patients. This effort uncovers a sequence-dependent splicing dysregulation in 36% of children linked to worse prognosis and a lower rate of complete remission. Surprisingly, this change in RNA splicing matches that induced by SRSF2 mutations, which are common in adult AML. Instead, we identify U2AF2 dysregulation as the driver of aberrant splicing in pediatric AML. The pathologic splicing changes are characterized by "weak" polypyrimidine tracts and are susceptible to modest U2AF2 reduction. These outcomes can be improved by pharmacologic modulation of PRMT enzymes. Overall, these findings highlight the importance of modulating splicing defects to improve treatment response in pediatric AML.

Indexed as

Drug Resistance, NeoplasmLeukemia, Myeloid, AcuteRNA SplicingChildChild, PreschoolFemaleHumansMaleMutationPrognosisSerine-Arginine Splicing FactorsSplicing Factor U2AFSerine-Arginine Splicing FactorsSplicing Factor U2AFSRSF2 protein, humanU2AF2 protein, humanpediatric acute myeloid leukemiaPRMT enzymessplicing dysregulationtherapy resistanceU2AF2 downregulation

Identifiers

PMID41564858
PMCPMC12866159

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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.