Epigenetics of Cutaneous T-cell Lymphoma: Biomarkers and Therapeutic Potentials

Overview

Journal Cancer Biol Med

Specialty Oncology

Date 2021 Feb 25

PMID 33628583

Citations 7

Authors

Pan Lai

Yang Wang

Affiliations

Soon will be listed here.

Abstract

Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of skin-homing non-Hodgkin lymphomas. There are limited options for effective treatment of patients with advanced-stage CTCL, leading to a poor survival rate. Epigenetics plays a pivotal role in regulating gene expression without altering the DNA sequence. Epigenetic alterations are involved in virtually all key cancer-associated pathways and are fundamental to the genesis of cancer. In recent years, the epigenetic hallmarks of CTCL have been gradually elucidated and their potential values in the diagnosis, prognosis, and therapeutic intervention have been clarified. In this review, we summarize the current knowledge of the best-studied epigenetic modifications in CTCL, including DNA methylation, histone modifications, microRNAs, and chromatin remodelers. These epigenetic regulators are essential in the development of CTCL and provide new insights into the clinical treatments of this refractory disease.

Citing Articles

Molecular techniques drive cutting edge advancements in management of cutaneous T cell lymphoma.

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Epigenetic Alterations in Canine Malignant Lymphoma: Future and Clinical Outcomes.

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References

Kebede A, Schneider R, Daujat S . Novel types and sites of histone modifications emerge as players in the transcriptional regulation contest. FEBS J. 2014; 282(9):1658-74. DOI: 10.1111/febs.13047. View

Kopp K, Ralfkiaer U, Gjerdrum L, Helvad R, Pedersen I, Litman T . STAT5-mediated expression of oncogenic miR-155 in cutaneous T-cell lymphoma. Cell Cycle. 2013; 12(12):1939-47. PMC: 3735708. DOI: 10.4161/cc.24987. View

Wu J, Wood G . Reduction of Fas/CD95 promoter methylation, upregulation of Fas protein, and enhancement of sensitivity to apoptosis in cutaneous T-cell lymphoma. Arch Dermatol. 2010; 147(4):443-9. DOI: 10.1001/archdermatol.2010.376. View

Schcolnik-Cabrera A, Dominguez-Gomez G, Duenas-Gonzalez A . Comparison of DNA demethylating and histone deacetylase inhibitors hydralazine-valproate versus vorinostat-decitabine incutaneous t-cell lymphoma in HUT78 cells. Am J Blood Res. 2018; 8(2):5-16. PMC: 6055069. View

Rozati S, Cheng P, Widmer D, Fujii K, Levesque M, Dummer R . Romidepsin and Azacitidine Synergize in their Epigenetic Modulatory Effects to Induce Apoptosis in CTCL. Clin Cancer Res. 2015; 22(8):2020-31. DOI: 10.1158/1078-0432.CCR-15-1435. View

Marstrand T, Ahler C, Ralfkiaer U, Clemmensen A, Kopp K, Sibbesen N . Validation of a diagnostic microRNA classifier in cutaneous T-cell lymphomas. Leuk Lymphoma. 2013; 55(4):957-8. DOI: 10.3109/10428194.2013.815352. View

Scarisbrick J, Mitchell T, Calonje E, Orchard G, Russell-Jones R, Whittaker S . Microsatellite instability is associated with hypermethylation of the hMLH1 gene and reduced gene expression in mycosis fungoides. J Invest Dermatol. 2003; 121(4):894-901. DOI: 10.1046/j.1523-1747.2003.12496.x. View

Kouzarides T . Chromatin modifications and their function. Cell. 2007; 128(4):693-705. DOI: 10.1016/j.cell.2007.02.005. View

Larsen F, Gundersen G, Lopez R, Prydz H . CpG islands as gene markers in the human genome. Genomics. 1992; 13(4):1095-107. DOI: 10.1016/0888-7543(92)90024-m. View

10.

Jones P, Baylin S . The fundamental role of epigenetic events in cancer. Nat Rev Genet. 2002; 3(6):415-28. DOI: 10.1038/nrg816. View

11.

Lee D, HAYES J, Pruss D, Wolffe A . A positive role for histone acetylation in transcription factor access to nucleosomal DNA. Cell. 1993; 72(1):73-84. DOI: 10.1016/0092-8674(93)90051-q. View

12.

Samimi S, Morrissey K, Anshelevich S, Evans K, Gardner J, Musiek A . Romidepsin and interferon gamma: a novel combination for refractory cutaneous T-cell lymphoma. J Am Acad Dermatol. 2012; 68(1):e5-6. DOI: 10.1016/j.jaad.2011.06.043. View

13.

Jones C, Wain E, Chu C, Tosi I, Foster R, McKenzie R . Downregulation of Fas gene expression in Sézary syndrome is associated with promoter hypermethylation. J Invest Dermatol. 2009; 130(4):1116-25. DOI: 10.1038/jid.2009.301. View

14.

Su M, Dorocicz I, Dragowska W, Ho V, Li G, Voss N . Aberrant expression of T-plastin in Sezary cells. Cancer Res. 2003; 63(21):7122-7. View

15.

Yi S, Sun J, Qiu L, Fu W, Wang A, Liu X . Dual Role of EZH2 in Cutaneous Anaplastic Large Cell Lymphoma: Promoting Tumor Cell Survival and Regulating Tumor Microenvironment. J Invest Dermatol. 2017; 138(5):1126-1136. DOI: 10.1016/j.jid.2017.10.036. View

16.

Pradeepa M, Grimes G, Kumar Y, Olley G, Taylor G, Schneider R . Histone H3 globular domain acetylation identifies a new class of enhancers. Nat Genet. 2016; 48(6):681-6. PMC: 4886833. DOI: 10.1038/ng.3550. View

17.

Hammond S, Bernstein E, Beach D, Hannon G . An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature. 2000; 404(6775):293-6. DOI: 10.1038/35005107. View

18.

Cristofoletti C, Picchio M, Lazzeri C, Tocco V, Pagani E, Bresin A . Comprehensive analysis of PTEN status in Sezary syndrome. Blood. 2013; 122(20):3511-20. DOI: 10.1182/blood-2013-06-510578. View

19.

Qiu L, Liu F, Yi S, Li X, Liu X, Xiao C . Loss of 5-Hydroxymethylcytosine Is an Epigenetic Biomarker in Cutaneous T-Cell Lymphoma. J Invest Dermatol. 2018; 138(11):2388-2397. DOI: 10.1016/j.jid.2018.05.007. View

20.

Du J, Johnson L, Jacobsen S, Patel D . DNA methylation pathways and their crosstalk with histone methylation. Nat Rev Mol Cell Biol. 2015; 16(9):519-32. PMC: 4672940. DOI: 10.1038/nrm4043. View