Characterization of the DNA copy-number genome in the blood of cutaneous T-cell lymphoma patients
- PMID: 21881587
- PMCID: PMC3841973
- DOI: 10.1038/jid.2011.254
Characterization of the DNA copy-number genome in the blood of cutaneous T-cell lymphoma patients
Abstract
Cutaneous T-cell lymphoma (CTCL) is a heterogeneous non-Hodgkin's lymphoma that may variably involve the skin, lymph nodes, and peripheral blood. Malignant burden ranges from cutaneous patches and plaques with little evidence of blood involvement to erythroderma often in association with frank leukemia, as in Sézary syndrome. Toward a better understanding of the pathogenesis of this CD4+ T-cell malignancy, we conducted a high-resolution genomic analysis combining DNA (23 samples) and mRNA (12 samples) data of peripheral blood isolates from CTCL patients across a spectrum of stages. Strikingly, even patients with limited involvement, e.g., normal CD4 counts, contained significant copy-number alterations. Defining genomic characteristics of CTCL blood involvement included gains on 8q and 17q, and deletions on 17p and chromosome 10. A consensus analysis of 108 leukemic CTCL samples demonstrated global similarities among patients with varied blood involvement, narrowing 38 of 62 loci. Toward an annotated framework for in vitro testing, we also characterized genomic alterations in five CTCL cell lines (HH, HUT78, PNO, SeAx, and Sez4), revealing intact core features of leukemic CTCL. Together, these studies produce the most comprehensive view of the leukemic CTCL genome to date, with implications for pathogenesis, molecular classification, and potential future therapeutic developments.
Conflict of interest statement
The authors state no conflict of interest.
Figures
Similar articles
-
Cutaneous T cell lymphoma: the helping hand of dendritic cells.Ann N Y Acad Sci. 2001 Sep;941:1-11. Ann N Y Acad Sci. 2001. PMID: 11594563 Review.
-
Epigenetic profiling of cutaneous T-cell lymphoma: promoter hypermethylation of multiple tumor suppressor genes including BCL7a, PTPRG, and p73.J Clin Oncol. 2005 Jun 10;23(17):3886-96. doi: 10.1200/JCO.2005.11.353. Epub 2005 May 16. J Clin Oncol. 2005. PMID: 15897551
-
Array-based CGH of primary cutaneous CD8+ aggressive EPIDERMO-tropic cytotoxic T-cell lymphoma.Genes Chromosomes Cancer. 2018 Dec;57(12):622-629. doi: 10.1002/gcc.22673. Epub 2018 Oct 11. Genes Chromosomes Cancer. 2018. PMID: 30307677
-
Primary T Cells from Cutaneous T-cell Lymphoma Skin Explants Display an Exhausted Immune Checkpoint Profile.Cancer Immunol Res. 2018 Aug;6(8):900-909. doi: 10.1158/2326-6066.CIR-17-0270. Epub 2018 Jun 12. Cancer Immunol Res. 2018. PMID: 29895574 Free PMC article.
-
Analysis of clonality in cutaneous T cell lymphoma and associated diseases.Ann N Y Acad Sci. 2001 Sep;941:26-30. Ann N Y Acad Sci. 2001. PMID: 11594579 Review.
Cited by
-
Transcriptomic and proteomic analysis of tumor suppressive effects of GZ17-6.02 against mycosis fungoides.Sci Rep. 2024 Jan 23;14(1):1955. doi: 10.1038/s41598-024-52544-z. Sci Rep. 2024. PMID: 38263212 Free PMC article.
-
FISH Panel for Leukemic Cutaneous T-Cell Lymphoma: Extended Patient Cohort Correlation with Blood Involvement and Clinical Outcomes.JID Innov. 2023 Jun 14;3(5):100212. doi: 10.1016/j.xjidi.2023.100212. eCollection 2023 Sep. JID Innov. 2023. PMID: 37674691 Free PMC article.
-
Blocking STAT3/5 through direct or upstream kinase targeting in leukemic cutaneous T-cell lymphoma.EMBO Mol Med. 2022 Dec 7;14(12):e15200. doi: 10.15252/emmm.202115200. Epub 2022 Nov 7. EMBO Mol Med. 2022. PMID: 36341492 Free PMC article.
-
Single-cell RNA-sequencing reveals predictive features of response to pembrolizumab in Sézary syndrome.Oncoimmunology. 2022 Aug 27;11(1):2115197. doi: 10.1080/2162402X.2022.2115197. eCollection 2022. Oncoimmunology. 2022. PMID: 36046812 Free PMC article.
-
Integrated transcriptome and trajectory analysis of cutaneous T-cell lymphoma identifies putative precancer populations.Blood Adv. 2023 Feb 14;7(3):445-457. doi: 10.1182/bloodadvances.2022008168. Blood Adv. 2023. PMID: 35947128 Free PMC article.
References
-
- Berger CL, Edelson RL. Current concepts of the immunobiology and immunotherapy of cutaneous T cell lymphoma: insights gained through cross-talk between the clinic and the bench. Leuk Lymphoma. 2003;44:1697–703. - PubMed
-
- Berger CL, Tigelaar R, Cohen J, et al. Cutaneous T-cell lymphoma: malignant proliferation of T-regulatory cells. Blood. 2005;105:1640–7. - PubMed
-
- Bernengo MG, Novelli M, Quaglino P, et al. The relevance of the CD4+ CD26− subset in the identification of circulating Sézary cells. Br J Dermatol. 2001;144:125–35. - PubMed
Publication types
MeSH terms
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Research Materials