Role of Dysregulated Cytokine Signaling and Bacterial Triggers in the Pathogenesis of Cutaneous T-Cell Lymphoma

Melania H. Fanok; Amy Sun; Laura K. Fogli; Vijay Narendran; Miriam Eckstein; Kasthuri Kannan; Igor Dolgalev; Charalampos Lazaris; Adriana Heguy; Mary E. Laird; Mark S. Sundrud; Cynthia Liu; Jeff Kutok; Rodrigo S. Lacruz; Jo Ann Latkowski; Iannis Aifantis; Niels Ødum; Kenneth B. Hymes; Swati Goel; Sergei B. Koralov

doi:10.1016/j.jid.2017.10.028

Role of Dysregulated Cytokine Signaling and Bacterial Triggers in the Pathogenesis of Cutaneous T-Cell Lymphoma

Melania H. Fanok, Amy Sun, Laura K. Fogli, Vijay Narendran, Miriam Eckstein, Kasthuri Kannan, Igor Dolgalev, Charalampos Lazaris, Adriana Heguy, Mary E. Laird, Mark S. Sundrud, Cynthia Liu, Jeff Kutok, Rodrigo S. Lacruz, Jo Ann Latkowski, Iannis Aifantis, Niels Ødum, Kenneth B. Hymes, Swati Goel, Sergei B. Koralov^*

^*Corresponding author af dette arbejde

29 Citationer (Scopus)

Abstract

Cutaneous T-cell lymphoma is a heterogeneous group of lymphomas characterized by the accumulation of malignant T cells in the skin. The molecular and cellular etiology of this malignancy remains enigmatic, and what role antigenic stimulation plays in the initiation and/or progression of the disease remains to be elucidated. Deep sequencing of the tumor genome showed a highly heterogeneous landscape of genetic perturbations, and transcriptome analysis of transformed T cells further highlighted the heterogeneity of this disease. Nonetheless, using data harvested from high-throughput transcriptional profiling allowed us to develop a reliable signature of this malignancy. Focusing on a key cytokine signaling pathway previously implicated in cutaneous T-cell lymphoma pathogenesis, JAK/STAT signaling, we used conditional gene targeting to develop a fully penetrant small animal model of this disease that recapitulates many key features of mycosis fungoides, a common variant of cutaneous T-cell lymphoma. Using this mouse model, we show that T-cell receptor engagement is critical for malignant transformation of the T lymphocytes and that progression of the disease is dependent on microbiota.

Originalsprog	Engelsk
Tidsskrift	Journal of Investigative Dermatology
Vol/bind	138
Udgave nummer	5
Sider (fra-til)	1116-1125
Antal sider	10
ISSN	0022-202X
DOI	https://doi.org/10.1016/j.jid.2017.10.028
Status	Udgivet - 2018

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10.1016/j.jid.2017.10.028

http://www.jidonline.org/article/S0022202X17331445/pdf

Citationsformater

Fanok, M. H., Sun, A., Fogli, L. K., Narendran, V., Eckstein, M., Kannan, K., Dolgalev, I., Lazaris, C., Heguy, A., Laird, M. E., Sundrud, M. S., Liu, C., Kutok, J., Lacruz, R. S., Latkowski, J. A., Aifantis, I., Ødum, N., Hymes, K. B., Goel, S., & Koralov, S. B. (2018). Role of Dysregulated Cytokine Signaling and Bacterial Triggers in the Pathogenesis of Cutaneous T-Cell Lymphoma. Journal of Investigative Dermatology, 138(5), 1116-1125. https://doi.org/10.1016/j.jid.2017.10.028

Fanok, MH, Sun, A, Fogli, LK, Narendran, V, Eckstein, M, Kannan, K, Dolgalev, I, Lazaris, C, Heguy, A, Laird, ME, Sundrud, MS, Liu, C, Kutok, J, Lacruz, RS, Latkowski, JA, Aifantis, I, Ødum, N, Hymes, KB, Goel, S & Koralov, SB 2018, 'Role of Dysregulated Cytokine Signaling and Bacterial Triggers in the Pathogenesis of Cutaneous T-Cell Lymphoma', Journal of Investigative Dermatology, bind 138, nr. 5, s. 1116-1125. https://doi.org/10.1016/j.jid.2017.10.028

@article{e7fd7eedf4fa46b0ae10d0adb1fcc26d,

title = "Role of Dysregulated Cytokine Signaling and Bacterial Triggers in the Pathogenesis of Cutaneous T-Cell Lymphoma",

abstract = "Cutaneous T-cell lymphoma is a heterogeneous group of lymphomas characterized by the accumulation of malignant T cells in the skin. The molecular and cellular etiology of this malignancy remains enigmatic, and what role antigenic stimulation plays in the initiation and/or progression of the disease remains to be elucidated. Deep sequencing of the tumor genome showed a highly heterogeneous landscape of genetic perturbations, and transcriptome analysis of transformed T cells further highlighted the heterogeneity of this disease. Nonetheless, using data harvested from high-throughput transcriptional profiling allowed us to develop a reliable signature of this malignancy. Focusing on a key cytokine signaling pathway previously implicated in cutaneous T-cell lymphoma pathogenesis, JAK/STAT signaling, we used conditional gene targeting to develop a fully penetrant small animal model of this disease that recapitulates many key features of mycosis fungoides, a common variant of cutaneous T-cell lymphoma. Using this mouse model, we show that T-cell receptor engagement is critical for malignant transformation of the T lymphocytes and that progression of the disease is dependent on microbiota.",

author = "Fanok, {Melania H.} and Amy Sun and Fogli, {Laura K.} and Vijay Narendran and Miriam Eckstein and Kasthuri Kannan and Igor Dolgalev and Charalampos Lazaris and Adriana Heguy and Laird, {Mary E.} and Sundrud, {Mark S.} and Cynthia Liu and Jeff Kutok and Lacruz, {Rodrigo S.} and Latkowski, {Jo Ann} and Iannis Aifantis and Niels {\O}dum and Hymes, {Kenneth B.} and Swati Goel and Koralov, {Sergei B.}",

year = "2018",

doi = "10.1016/j.jid.2017.10.028",

language = "English",

volume = "138",

pages = "1116--1125",

journal = "Journal of Investigative Dermatology",

issn = "0022-202X",

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TY - JOUR

T1 - Role of Dysregulated Cytokine Signaling and Bacterial Triggers in the Pathogenesis of Cutaneous T-Cell Lymphoma

AU - Fanok, Melania H.

AU - Sun, Amy

AU - Fogli, Laura K.

AU - Narendran, Vijay

AU - Eckstein, Miriam

AU - Kannan, Kasthuri

AU - Dolgalev, Igor

AU - Lazaris, Charalampos

AU - Heguy, Adriana

AU - Laird, Mary E.

AU - Sundrud, Mark S.

AU - Liu, Cynthia

AU - Kutok, Jeff

AU - Lacruz, Rodrigo S.

AU - Latkowski, Jo Ann

AU - Aifantis, Iannis

AU - Ødum, Niels

AU - Hymes, Kenneth B.

AU - Goel, Swati

AU - Koralov, Sergei B.

PY - 2018

Y1 - 2018

N2 - Cutaneous T-cell lymphoma is a heterogeneous group of lymphomas characterized by the accumulation of malignant T cells in the skin. The molecular and cellular etiology of this malignancy remains enigmatic, and what role antigenic stimulation plays in the initiation and/or progression of the disease remains to be elucidated. Deep sequencing of the tumor genome showed a highly heterogeneous landscape of genetic perturbations, and transcriptome analysis of transformed T cells further highlighted the heterogeneity of this disease. Nonetheless, using data harvested from high-throughput transcriptional profiling allowed us to develop a reliable signature of this malignancy. Focusing on a key cytokine signaling pathway previously implicated in cutaneous T-cell lymphoma pathogenesis, JAK/STAT signaling, we used conditional gene targeting to develop a fully penetrant small animal model of this disease that recapitulates many key features of mycosis fungoides, a common variant of cutaneous T-cell lymphoma. Using this mouse model, we show that T-cell receptor engagement is critical for malignant transformation of the T lymphocytes and that progression of the disease is dependent on microbiota.

AB - Cutaneous T-cell lymphoma is a heterogeneous group of lymphomas characterized by the accumulation of malignant T cells in the skin. The molecular and cellular etiology of this malignancy remains enigmatic, and what role antigenic stimulation plays in the initiation and/or progression of the disease remains to be elucidated. Deep sequencing of the tumor genome showed a highly heterogeneous landscape of genetic perturbations, and transcriptome analysis of transformed T cells further highlighted the heterogeneity of this disease. Nonetheless, using data harvested from high-throughput transcriptional profiling allowed us to develop a reliable signature of this malignancy. Focusing on a key cytokine signaling pathway previously implicated in cutaneous T-cell lymphoma pathogenesis, JAK/STAT signaling, we used conditional gene targeting to develop a fully penetrant small animal model of this disease that recapitulates many key features of mycosis fungoides, a common variant of cutaneous T-cell lymphoma. Using this mouse model, we show that T-cell receptor engagement is critical for malignant transformation of the T lymphocytes and that progression of the disease is dependent on microbiota.

U2 - 10.1016/j.jid.2017.10.028

DO - 10.1016/j.jid.2017.10.028

M3 - Journal article

C2 - 29128259

AN - SCOPUS:85044742236

SN - 0022-202X

VL - 138

SP - 1116

EP - 1125

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

IS - 5

ER -

Role of Dysregulated Cytokine Signaling and Bacterial Triggers in the Pathogenesis of Cutaneous T-Cell Lymphoma

Abstract

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