Evidence map›Paper›PMID 42090514›Full record

ArticleScience advances2026

ATRA improves megakaryopoiesis in immune thrombocytopenia through up-regulating the HIF-1α/SPHK2/S1P pathway.

Qiu-Sha Huang, Jing Xue, Feng-Qi Liu, Qi Chen, Gaochao Zhang, Xue-Yan Sun, Chencong Wang, Liping Yang, Yu Hou, Yueying Li and 9 more

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In one paragraph

Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Qiu-Sha HuangPeking University People's Hospital, Peking University Institute of Hematology, Beijing, China.ORCID 0009-0001-7797-700X
Jing XuePeking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
Feng-Qi LiuPeking University People's Hospital, Peking University Institute of Hematology, Beijing, China.ORCID 0000-0002-7504-2243
Qi ChenPeking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
Gaochao ZhangPeking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
Xue-Yan SunPeking University People's Hospital, Peking University Institute of Hematology, Beijing, China.ORCID 0000-0001-5176-8472
Chencong WangPeking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
Liping YangPeking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
Yu HouDepartment of Hematology, Qilu Hospital, Jinan, China.
Yueying LiChinese Academy of Sciences (CAS) Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, CAS, Beijing, China.
Qianfei WangChinese Academy of Sciences (CAS) Key Laboratory of Genomic and Precision Medicine, Collaborative Innovation Center of Genetics and Development, Beijing Institute of Genomics, CAS, Beijing, China.
Jun PengDepartment of Hematology, Qilu Hospital, Jinan, China.
Ming HouDepartment of Hematology, Qilu Hospital, Jinan, China.
Xiaosu ZhaoPeking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
Yuan KongPeking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
Yingjun ChangPeking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
Xiangyu ZhaoPeking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
Xiao-Jun HuangPeking University People's Hospital, Peking University Institute of Hematology, Beijing, China.ORCID 0000-0002-2145-6643
Xiao-Hui ZhangPeking University People's Hospital, Peking University Institute of Hematology, Beijing, China.ORCID 0000-0003-4730-256X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Our previous clinical studies show that all-trans retinoic acid (ATRA) induces a sustained response in patients with immune thrombocytopenia (ITP). However, its mechanisms of action remain unclear. In this study, we observed disorganized cytoskeleton and impaired proplatelet formation (PPF) in megakaryocytes from patients with ITP. Metabolite profiling revealed reduced sphingosine 1-phosphate (S1P) levels in ITP. Decreased sphingosine kinase 2 (SPHK2) expression was responsible for the low S1P levels in ITP. In addition, S1P was essential for activating S1P receptor 1 and Rac1, which regulate cytoskeletal reorganization and PPF. Furthermore, hypoxia-inducible factor-1α (HIF-1α) was shown to mediate SPHK2 and S1P production. Decreased HIF-1α expression in megakaryocytes from patients with ITP contributed to impaired PPF. We subsequently found that ATRA up-regulated HIF-1α and corrected impaired PPF in vitro and in vivo. These findings reveal that ATRA targets the HIF-1α/SPHK2/S1P pathway to improve PPF dysfunction, offering mechanistic insights into its clinical efficacy in ITP.

Indexed as

Hypoxia-Inducible Factor 1, alpha SubunitLysophospholipidsMegakaryocytesPhosphotransferases (Alcohol Group Acceptor)Purpura, Thrombocytopenic, IdiopathicSignal TransductionSphingosineThrombopoiesisTretinoinAnimalsBlood PlateletsHumansrac1 GTP-Binding ProteinSphingosine KinaseUp-RegulationHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitLysophospholipidsPhosphotransferases (Alcohol Group Acceptor)rac1 GTP-Binding ProteinSphingosinesphingosine 1-phosphateSphingosine Kinasesphingosine kinase 2, humanTretinoin

Identifiers

PMID42090514
PMCPMC13148329

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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.