Evidence map›Paper›PMID 38326887›Full record

ArticleExperimental hematology & oncology2024

The HSP90-MYC-CDK9 network drives therapeutic resistance in mantle cell lymphoma.

Fangfang Yan, Vivian Jiang, Alexa Jordan, Yuxuan Che, Yang Liu, Qingsong Cai, Yu Xue, Yijing Li, Joseph McIntosh, Zhihong Chen and 13 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Experimental hematology & oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
6.2field-weighted citation impact, top 3% 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

11 citing papers in PubMed, 22 citations in OpenAlex.

  1. Review
  2. [Advances in single cell omics applications in mantle cell lymphoma].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026
    Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. CAR-T cell combination therapies in hematologic malignancies.Experimental hematology & oncology · 2024
    Review
  11. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 3 institutions in 1 country.

Fangfang Yan *Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
Vivian Jiang *Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. cjiang@mdanderson.org.
Alexa JordanDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yuxuan CheDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yang LiuDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Qingsong CaiDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yu XueDepartment of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
Yijing LiDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Joseph McIntoshDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Zhihong ChenDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jovanny VargasDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lei NieDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yixin YaoDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Heng-Huan LeeDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Wei WangDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
JohnNelson R BigcalDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Maria BadilloDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jitendra MeenaVerna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, 77030, USA.
Christopher FlowersDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jia ZhouDepartment of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, 77555, USA.
Zhongming ZhaoCenter for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA. Zhongming.Zhao@uth.tmc.edu.
Lukas M SimonTherapeutic Innovation Center, Baylor College of Medicine, Houston, TX, 77030, USA. Lukas.Simon@bcm.edu.
Michael Wang *Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. miwang@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USBaylor College of Medicine · USThe University of Texas Medical Branch at Galveston · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Transforming dbGaP genetic and genomic data to FAIR-ready by artificial intelligence and machine learning algorithmsR01LM012806 · NLM · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI Zhongming Zhao · 2017 to 2026
$3.7M
NCI NIH HHS P30 CA016672NIH HHS R01LM012806NLM NIH HHS R01 LM012806
6 · The paper itself

Abstract

Brexucabtagene autoleucel CAR-T therapy is highly efficacious in overcoming resistance to Bruton's tyrosine kinase inhibitors (BTKi) in mantle cell lymphoma. However, many patients relapse post CAR-T therapy with dismal outcomes. To dissect the underlying mechanisms of sequential resistance to BTKi and CAR-T therapy, we performed single-cell RNA sequencing analysis for 66 samples from 25 patients treated with BTKi and/or CAR-T therapy and conducted in-depth bioinformatics™ analysis. Our analysis revealed that MYC activity progressively increased with sequential resistance. HSP90AB1 (Heat shock protein 90 alpha family class B member 1), a MYC target, was identified as early driver of CAR-T resistance. CDK9 (Cyclin-dependent kinase 9), another MYC target, was significantly upregulated in Dual-R samples. Both HSP90AB1 and CDK9 expression were correlated with MYC activity levels. Pharmaceutical co-targeting of HSP90 and CDK9 synergistically diminished MYC activity, leading to potent anti-MCL activity. Collectively, our study revealed that HSP90-MYC-CDK9 network is the primary driving force of therapeutic resistance.

Indexed as

CAR-T therapyMantle cell lymphomaResistanceSingle-cell RNA sequencing

Identifiers

PMID38326887
PMCPMC10848414
OpenAlexW4391613908

What OpenQuestion holds

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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.