Multimodal single-cell analysis of cutaneous T-cell lymphoma reveals distinct subclonal tissue-dependent signatures
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Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of mature T-cell neoplasms characterized by the accumulation of clonal malignant CD4+ T cells in the skin. The most common variant of CTCL, mycosis fungoides (MF ), is confined to the skin in early stages but can be accompanied by extracutaneous dissemination of malignant T cells to the blood and lymph nodes in advanced stages of disease. Sézary syndrome (SS), a leukemic form of disease, is characterized by significant blood involvement. Little is known about the transcriptional and genomic relationship between skin- and blood-residing malignant T cells in CTCL. To identify and interrogate malignant clones in matched skin and blood from patients with leukemic MF and SS, we combine T-cell receptor clonotyping with quantification of gene expression and cell surface markers at the single cell level. Our data reveal clonal evolution at a transcriptional and genetic level within the malignant populations of individual patients. We highlight highly consistent transcriptional signatures delineating skin- and blood-derived malignant T cells. Analysis of these 2 populations suggests that environmental cues, along with genetic aberrations, contribute to transcriptional profiles of malignant T cells. Our findings indicate that the skin microenvironment in CTCL promotes a transcriptional response supporting rapid malignant expansion, as opposed to the quiescent state observed in the blood, potentially influencing efficacy of therapies. These results provide insight into tissue-specific characteristics of cancerous cells and underscore the need to address the patients' individual malignant profiles at the time of therapy to eliminate all subclones.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Blood |
| Vol/bind | 138 |
| Udgave nummer | 16 |
| Sider (fra-til) | 1456-1464 |
| Antal sider | 9 |
| ISSN | 0006-4971 |
| DOI | |
| Status | Udgivet - 2021 |
Bibliografisk note
Funding Information:
The authors thank New York University Genome Technology Center for technical assistance and support. S.B.K. was supported by the National Institutes of Health, National Heart, Lung, and Blood Institute R01 grant (HL-125816), LEO Foundation grant (LF-OC-20-000351), New York University Cancer Center pilot grant (P30CA016087), the Judith and Stewart Colton Center for Autoimmunity pilot grant, and a grant from the Drs. Martin and Dorothy Spatz Foundation. A.S. was supported by HHMI Medical Scholar Fellowship. P.S. was supported by the National Institutes of Health, National Human Genome Research Institute (R21HG009748) and the Chan Zuckerberg Initiative (HCA-A-1704-01895). T.B.B. and N.?. were supported by the Danish Cancer Society (Kr?ftens Bek?mpelse), the Danish Council for Independent Research (Danmarks Frie Forskningsfond), and the LEO Foundation. M.E.K. was supported by a grant from the Drs. Martin and Dorothy Spatz Foundation.
Funding Information:
S.B.K. was supported by the National Institutes of Health, National Heart, Lung, and Blood Institute R01 grant (HL-125816), LEO Foundation grant (LF-OC-20-000351), New York University Cancer Center pilot grant (P30CA016087), the Judith and Stewart Colton Center for Autoimmunity pilot grant, and a grant from the Drs. Martin and Dorothy Spatz Foundation. A.S. was supported by HHMI Medical Scholar Fellowship. P.S. was supported by the National Institutes of Health, National Human Genome Research Institute (R21HG009748) and the Chan Zuckerberg Initiative (HCA-A-1704-01895). T.B.B. and N.Ø. were supported by the Danish Cancer Society (Kræftens Bekæmpelse), the Danish Council for Independent Research (Danmarks Frie Forskningsfond), and the LEO Foundation. M.E.K. was supported by a grant from the Drs. Martin and Dorothy Spatz Foundation.
Publisher Copyright:
© 2021 American Society of Hematology
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