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Skin colonization by circulating neoplastic clones in cutaneous T-cell lymphoma

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Harvard

Iyer, A, Hennessey, D, O'Keefe, S, Patterson, J, Wang, W, Wong, GK-S & Gniadecki, R 2019, 'Skin colonization by circulating neoplastic clones in cutaneous T-cell lymphoma' Blood, vol. 134, no. 18, pp. 1517-1527. https://doi.org/10.1182/blood.2019002516

APA

Iyer, A., Hennessey, D., O'Keefe, S., Patterson, J., Wang, W., Wong, G. K-S., & Gniadecki, R. (2019). Skin colonization by circulating neoplastic clones in cutaneous T-cell lymphoma. Blood, 134(18), 1517-1527. https://doi.org/10.1182/blood.2019002516

CBE

Iyer A, Hennessey D, O'Keefe S, Patterson J, Wang W, Wong GK-S, Gniadecki R. 2019. Skin colonization by circulating neoplastic clones in cutaneous T-cell lymphoma. Blood. 134(18):1517-1527. https://doi.org/10.1182/blood.2019002516

MLA

Vancouver

Iyer A, Hennessey D, O'Keefe S, Patterson J, Wang W, Wong GK-S et al. Skin colonization by circulating neoplastic clones in cutaneous T-cell lymphoma. Blood. 2019 Oct 31;134(18):1517-1527. https://doi.org/10.1182/blood.2019002516

Author

Iyer, Aishwarya ; Hennessey, Dylan ; O'Keefe, Sandra ; Patterson, Jordan ; Wang, Weiwei ; Wong, Gane Ka-Shu ; Gniadecki, Robert. / Skin colonization by circulating neoplastic clones in cutaneous T-cell lymphoma. In: Blood. 2019 ; Vol. 134, No. 18. pp. 1517-1527.

Bibtex

@article{08175287b0934e14a9f186283e34b4ba,
title = "Skin colonization by circulating neoplastic clones in cutaneous T-cell lymphoma",
abstract = "Mycosis fungoides (MF) is a mature T-cell lymphoma currently thought to develop primarily in the skin by a clonal expansion of a transformed, resident memory T cell. However, this concept does not explain the key characteristics of MF, such as the debut with multiple, widespread skin lesions or inability of skin-directed therapies to provide cure. The testable inference of the mature T-cell theory is the clonality of MF with respect to all rearranged T-cell receptor (TCR) genes. Here, we used a whole-exome sequencing approach to detect and quantify TCR-α, β, and γ clonotypes in tumor cell clusters microdissected from MF lesions. This method allowed us to calculate the tumor cell fraction of the sample and therefore an unequivocal identification of the TCR clonotypes as neoplastic. Analysis of TCR sequences from 29 patients with MF stage I to IV proved the existence of multiple T-cell clones within the tumor cell fraction, with a considerable variation between patients and between lesions from the same patient (median, 11 clones; range, 2-80 clones/sample). We have also detected multiple neoplastic clones in the peripheral blood in all examined patients. Based on these findings, we propose that circulating neoplastic T-cell clones continuously replenish the lesions of MF, thus increasing their heterogeneity by a mechanism analogous to the consecutive tumor seeding. We hypothesize that circulating neoplastic clones might be a promising target for therapy and could be exploited as a potential biomarker in MF.",
author = "Aishwarya Iyer and Dylan Hennessey and Sandra O'Keefe and Jordan Patterson and Weiwei Wang and Wong, {Gane Ka-Shu} and Robert Gniadecki",
note = "{\circledC} 2019 by The American Society of Hematology.",
year = "2019",
month = "10",
day = "31",
doi = "10.1182/blood.2019002516",
language = "English",
volume = "134",
pages = "1517--1527",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "18",

}

RIS

TY - JOUR

T1 - Skin colonization by circulating neoplastic clones in cutaneous T-cell lymphoma

AU - Iyer, Aishwarya

AU - Hennessey, Dylan

AU - O'Keefe, Sandra

AU - Patterson, Jordan

AU - Wang, Weiwei

AU - Wong, Gane Ka-Shu

AU - Gniadecki, Robert

N1 - © 2019 by The American Society of Hematology.

PY - 2019/10/31

Y1 - 2019/10/31

N2 - Mycosis fungoides (MF) is a mature T-cell lymphoma currently thought to develop primarily in the skin by a clonal expansion of a transformed, resident memory T cell. However, this concept does not explain the key characteristics of MF, such as the debut with multiple, widespread skin lesions or inability of skin-directed therapies to provide cure. The testable inference of the mature T-cell theory is the clonality of MF with respect to all rearranged T-cell receptor (TCR) genes. Here, we used a whole-exome sequencing approach to detect and quantify TCR-α, β, and γ clonotypes in tumor cell clusters microdissected from MF lesions. This method allowed us to calculate the tumor cell fraction of the sample and therefore an unequivocal identification of the TCR clonotypes as neoplastic. Analysis of TCR sequences from 29 patients with MF stage I to IV proved the existence of multiple T-cell clones within the tumor cell fraction, with a considerable variation between patients and between lesions from the same patient (median, 11 clones; range, 2-80 clones/sample). We have also detected multiple neoplastic clones in the peripheral blood in all examined patients. Based on these findings, we propose that circulating neoplastic T-cell clones continuously replenish the lesions of MF, thus increasing their heterogeneity by a mechanism analogous to the consecutive tumor seeding. We hypothesize that circulating neoplastic clones might be a promising target for therapy and could be exploited as a potential biomarker in MF.

AB - Mycosis fungoides (MF) is a mature T-cell lymphoma currently thought to develop primarily in the skin by a clonal expansion of a transformed, resident memory T cell. However, this concept does not explain the key characteristics of MF, such as the debut with multiple, widespread skin lesions or inability of skin-directed therapies to provide cure. The testable inference of the mature T-cell theory is the clonality of MF with respect to all rearranged T-cell receptor (TCR) genes. Here, we used a whole-exome sequencing approach to detect and quantify TCR-α, β, and γ clonotypes in tumor cell clusters microdissected from MF lesions. This method allowed us to calculate the tumor cell fraction of the sample and therefore an unequivocal identification of the TCR clonotypes as neoplastic. Analysis of TCR sequences from 29 patients with MF stage I to IV proved the existence of multiple T-cell clones within the tumor cell fraction, with a considerable variation between patients and between lesions from the same patient (median, 11 clones; range, 2-80 clones/sample). We have also detected multiple neoplastic clones in the peripheral blood in all examined patients. Based on these findings, we propose that circulating neoplastic T-cell clones continuously replenish the lesions of MF, thus increasing their heterogeneity by a mechanism analogous to the consecutive tumor seeding. We hypothesize that circulating neoplastic clones might be a promising target for therapy and could be exploited as a potential biomarker in MF.

U2 - 10.1182/blood.2019002516

DO - 10.1182/blood.2019002516

M3 - Journal article

VL - 134

SP - 1517

EP - 1527

JO - Blood

JF - Blood

SN - 0006-4971

IS - 18

ER -

ID: 59268043