Role of Dysregulated Cytokine Signaling and Bacterial Triggers in the Pathogenesis of Cutaneous T-Cell Lymphoma
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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, 2018, p. 1116-1125.Research output: Contribution to journal › Journal article › Research › peer-review
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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
VL - 138
SP - 1116
EP - 1125
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 5
ER -
ID: 208883597