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

Research output: Contribution to journalArticle

10 Citations (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.

Original languageEnglish (US)
Pages (from-to)1116-1125
Number of pages10
JournalJournal of Investigative Dermatology
Volume138
Issue number5
DOIs
StatePublished - May 1 2018

Fingerprint

Cutaneous T-Cell Lymphoma
T-cells
Cytokines
T-Lymphocytes
Disease Progression
Animal Disease Models
High-Throughput Nucleotide Sequencing
Neoplasms
Mycosis Fungoides
Gene Targeting
Microbiota
Gene Expression Profiling
T-Cell Antigen Receptor
Lymphoma
Genes
Genome
Skin
Tumors
Animals
Throughput

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Fanok, M. H., Sun, A., Fogli, L. K., Narendran, V., Eckstein, M., Kannan, K., ... 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

Role of Dysregulated Cytokine Signaling and Bacterial Triggers in the Pathogenesis of Cutaneous T-Cell Lymphoma. / Fanok, Melania H.; Sun, Amy; Fogli, Laura K.; Narendran, Vijay; Eckstein, Miriam; Kannan, Kasthuri; Dolgalev, Igor; Lazaris, Charalampos; Heguy, Adriana; Laird, Mary E.; Sundrud, Mark S.; Liu, Cynthia; Kutok, Jeff; Lacruz, Rodrigo S.; Latkowski, Jo Ann; Aifantis, Iannis; Ødum, Niels; Hymes, Kenneth B.; Goel, Swati; Koralov, Sergei B.

In: Journal of Investigative Dermatology, Vol. 138, No. 5, 01.05.2018, p. 1116-1125.

Research output: Contribution to journalArticle

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, vol. 138, no. 5, pp. 1116-1125. https://doi.org/10.1016/j.jid.2017.10.028
Fanok, Melania H. ; Sun, Amy ; Fogli, Laura K. ; Narendran, Vijay ; Eckstein, Miriam ; Kannan, Kasthuri ; Dolgalev, Igor ; Lazaris, Charalampos ; Heguy, Adriana ; Laird, Mary E. ; Sundrud, Mark S. ; Liu, Cynthia ; Kutok, Jeff ; Lacruz, Rodrigo S. ; Latkowski, Jo Ann ; Aifantis, Iannis ; Ødum, Niels ; Hymes, Kenneth B. ; Goel, Swati ; Koralov, Sergei B. / Role of Dysregulated Cytokine Signaling and Bacterial Triggers in the Pathogenesis of Cutaneous T-Cell Lymphoma. In: Journal of Investigative Dermatology. 2018 ; Vol. 138, No. 5. pp. 1116-1125.
@article{2ad6f8612133487497161b8925d1aa05,
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",
month = "5",
day = "1",
doi = "10.1016/j.jid.2017.10.028",
language = "English (US)",
volume = "138",
pages = "1116--1125",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "5",

}

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 - 2018/5/1

Y1 - 2018/5/1

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.

UR - http://www.scopus.com/inward/record.url?scp=85044742236&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85044742236&partnerID=8YFLogxK

U2 - 10.1016/j.jid.2017.10.028

DO - 10.1016/j.jid.2017.10.028

M3 - Article

C2 - 29128259

AN - SCOPUS:85044742236

VL - 138

SP - 1116

EP - 1125

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 5

ER -