ArticleEBioMedicine2019
Novel cell adhesion/migration pathways are predictive markers of HDAC inhibitor resistance in cutaneous T cell lymphoma.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 36 citations in OpenAlex.
- From molecular pathogenesis to novel Therapeutic approaches - a review of recent advances in the treatment of peripheral T cell Lymphomas.Biomarker research · 2026Review
- LyP vs advanced-stage CTCLs: single-cell profiling reveals markers of self-limited vs aggressive disease behavior.Blood advances · 2026Article
- Insulin enables acquisition of the IL7RCell death & disease · 2026Article
- A Six-year Response to Belinostat in a Highly Probable Case of Relapsed/Refractory MF/SS Initially Classified as PTCL-NOS: A Case Report.OncoTargets and therapy · 2026Article
- LAIR1 prevents excess inflammatory tissue damage in Staphylococcus aureus skin infection and Cutaneous T-cell Lymphoma.JCI insight · 2025Article
- Inhibitory pattern recognition receptors: lessons from LAIR1.Nature reviews. Immunology · 2025Review
- Targeting LAIR1-mediated immunosuppression adds a new weapon to our immunotherapy arsenal.The Journal of clinical investigation · 2025Article
- Single-cell RNA sequencing comparison of CD4+, CD8+ and T-cell receptor γδ+ cutaneous T-cell lymphomas reveals subset-specific molecular phenotypes.The British journal of dermatology · 2025Article
- H3K14: A histone site closely related to diseases.Journal of Cancer · 2025Review
- Thioredoxin Domain Containing 5 (TXNDC5): Friend or Foe?Current issues in molecular biology · 2024Review
- GATA-3-dependent Gene Transcription is Impaired upon HDAC Inhibition.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- The role and mechanism of TXNDC5 in disease progression.Frontiers in immunology · 2024Review
- Single-cell analysis of Sézary syndrome reveals novel markers and shifting gene profiles associated with treatment.Blood advances · 2023Article
- The role and mechanism of TXNDC5 in diseases.European journal of medical research · 2022Review
- PEG10 amplification at 7q21.3 potentiates large-cell transformation in cutaneous T-cell lymphoma.Blood · 2022Article
- Genome-wide identification of alternative splicing associated with histone deacetylase inhibitor in cutaneous T-cell lymphomas.Frontiers in genetics · 2022Article
- DOT1L inhibition does not modify the sensitivity of cutaneous T cell lymphoma to pan-HDAC inhibitorsFrontiers in genetics · 2022Article
- Retrospective Analysis of 118 Patients With Cutaneous T-Cell Lymphomas: A Single-Center Experience.Frontiers in oncology · 2022Article
- Functional Depletion of HSP72 by siRNA and Quercetin Enhances Vorinostat-Induced Apoptosis in an HSP72-Overexpressing Cutaneous T-Cell Lymphoma Cell Line, Hut78.International journal of molecular sciences · 2021Article
- Epigenetics of cutaneous T-cell lymphoma: biomarkers and therapeutic potentials.Cancer biology & medicine · 2021Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundTreatment for Cutaneous T Cell Lymphoma (CTCL) is generally not curative. Therefore, selecting therapy that is effective and tolerable is critical to clinical decision-making. Histone deacetylase inhibitors (HDACi), epigenetic modifier drugs, are commonly used but effective in only ~30% of patients. There are no predictive markers of HDACi response and the CTCL histone acetylation landscape remains unmapped. We sought to identify pre-treatment molecular markers of resistance in CTCL that progressed on HDACi therapy.
methodsPurified T cells from 39 pre/post-treatment peripheral blood samples and skin biopsies from 20 patients were subjected to RNA-seq and ChIP-seq for histone acetylation marks (H3K14/9 ac, H3K27ac). We correlated significant differences in histone acetylation with gene expression in HDACi-resistant/sensitive CTCL. We extended these findings in additional CTCL patient cohorts (RNA-seq, microarray) and using ELISA in matched CTCL patient plasma.
findingsResistant CTCL exhibited high levels of histone acetylation, which correlated with increased expression of 338 genes (FDR < 0·05), including some novel to CTCL: BIRC5 (anti-apoptotic); RRM2 (cell cycle); TXNDC5, GSTM1 (redox); and CXCR4, LAIR2 (cell adhesion/migration). Several of these, including LAIR2, were elevated pre-treatment in HDACi-resistant CTCL. In CTCL patient plasma (n = 6), LAIR2 protein was also elevated (p < 0·01) compared to controls.
interpretationThis study is the first to connect genome-wide differences in chromatin acetylation and gene expression to HDACi-resistance in primary CTCL. Our results identify novel markers with high pre-treatment expression, such as LAIR2, as potential prognostic and/or predictors of HDACi-resistance in CTCL.
fundingNIH:CA156690, CA188286; NCATS: WU-ICTS UL1 TR000448; Siteman Cancer Center: CA091842.
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