Multimodal single-cell analysis of cutaneous T-cell lymphoma reveals distinct subclonal tissue-dependent signatures

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Multimodal single-cell analysis of cutaneous T-cell lymphoma reveals distinct subclonal tissue-dependent signatures. / Herrera, Alberto; Cheng, Anthony; Mimitou, Eleni P.; Seffens, Angelina; George, Dean; Bar-Natan, Michal; Heguy, Adriana; Ruggles, Kelly V.; Scher, Jose U.; Hymes, Kenneth; Latkowski, Jo Ann; Ødum, Niels; Kadin, Marshall E.; Ouyang, Zhengqing; Geskin, Larisa J.; Smibert, Peter; Buus, Terkild B.; Koralov, Sergei B.

In: Blood, Vol. 138, No. 16, 2021, p. 1456-1464.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Herrera, A, Cheng, A, Mimitou, EP, Seffens, A, George, D, Bar-Natan, M, Heguy, A, Ruggles, KV, Scher, JU, Hymes, K, Latkowski, JA, Ødum, N, Kadin, ME, Ouyang, Z, Geskin, LJ, Smibert, P, Buus, TB & Koralov, SB 2021, 'Multimodal single-cell analysis of cutaneous T-cell lymphoma reveals distinct subclonal tissue-dependent signatures', Blood, vol. 138, no. 16, pp. 1456-1464. https://doi.org/10.1182/blood.2020009346

APA

Herrera, A., Cheng, A., Mimitou, E. P., Seffens, A., George, D., Bar-Natan, M., Heguy, A., Ruggles, K. V., Scher, J. U., Hymes, K., Latkowski, J. A., Ødum, N., Kadin, M. E., Ouyang, Z., Geskin, L. J., Smibert, P., Buus, T. B., & Koralov, S. B. (2021). Multimodal single-cell analysis of cutaneous T-cell lymphoma reveals distinct subclonal tissue-dependent signatures. Blood, 138(16), 1456-1464. https://doi.org/10.1182/blood.2020009346

Vancouver

Herrera A, Cheng A, Mimitou EP, Seffens A, George D, Bar-Natan M et al. Multimodal single-cell analysis of cutaneous T-cell lymphoma reveals distinct subclonal tissue-dependent signatures. Blood. 2021;138(16):1456-1464. https://doi.org/10.1182/blood.2020009346

Author

Herrera, Alberto ; Cheng, Anthony ; Mimitou, Eleni P. ; Seffens, Angelina ; George, Dean ; Bar-Natan, Michal ; Heguy, Adriana ; Ruggles, Kelly V. ; Scher, Jose U. ; Hymes, Kenneth ; Latkowski, Jo Ann ; Ødum, Niels ; Kadin, Marshall E. ; Ouyang, Zhengqing ; Geskin, Larisa J. ; Smibert, Peter ; Buus, Terkild B. ; Koralov, Sergei B. / Multimodal single-cell analysis of cutaneous T-cell lymphoma reveals distinct subclonal tissue-dependent signatures. In: Blood. 2021 ; Vol. 138, No. 16. pp. 1456-1464.

Bibtex

@article{76c2146d4eeb4ee5883f870e256b7e02,
title = "Multimodal single-cell analysis of cutaneous T-cell lymphoma reveals distinct subclonal tissue-dependent signatures",
abstract = "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. S{\'e}zary 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.",
author = "Alberto Herrera and Anthony Cheng and Mimitou, {Eleni P.} and Angelina Seffens and Dean George and Michal Bar-Natan and Adriana Heguy and Ruggles, {Kelly V.} and Scher, {Jose U.} and Kenneth Hymes and Latkowski, {Jo Ann} and Niels {\O}dum and Kadin, {Marshall E.} and Zhengqing Ouyang and Geskin, {Larisa J.} and Peter Smibert and Buus, {Terkild B.} and Koralov, {Sergei B.}",
note = "Publisher Copyright: {\textcopyright} 2021 American Society of Hematology",
year = "2021",
doi = "10.1182/blood.2020009346",
language = "English",
volume = "138",
pages = "1456--1464",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "16",

}

RIS

TY - JOUR

T1 - Multimodal single-cell analysis of cutaneous T-cell lymphoma reveals distinct subclonal tissue-dependent signatures

AU - Herrera, Alberto

AU - Cheng, Anthony

AU - Mimitou, Eleni P.

AU - Seffens, Angelina

AU - George, Dean

AU - Bar-Natan, Michal

AU - Heguy, Adriana

AU - Ruggles, Kelly V.

AU - Scher, Jose U.

AU - Hymes, Kenneth

AU - Latkowski, Jo Ann

AU - Ødum, Niels

AU - Kadin, Marshall E.

AU - Ouyang, Zhengqing

AU - Geskin, Larisa J.

AU - Smibert, Peter

AU - Buus, Terkild B.

AU - Koralov, Sergei B.

N1 - Publisher Copyright: © 2021 American Society of Hematology

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1182/blood.2020009346

DO - 10.1182/blood.2020009346

M3 - Journal article

C2 - 34232982

AN - SCOPUS:85117086581

VL - 138

SP - 1456

EP - 1464

JO - Blood

JF - Blood

SN - 0006-4971

IS - 16

ER -

ID: 284196040