SATB1 in malignant T cells

Simon Mayland Fredholm; Andreas Willerslev-Olsen; Özcan Met; Linda Kubat; Maria Gluud; Sarah L. Mathiasen; Christina Friese; Edda Blümel; David Leander Petersen; Tengpeng Hu; Claudia Nastasi; Lise M. Lindahl; Terkild Brink Buus; Thorbjørn Frej Krejsgaard; Mariusz A. Wasik; Katharina Luise Maria Kopp; Sergei B. Koralov; Jenny L. Persson; Charlotte Menne Bonefeld; Carsten Geisler; Anders Woetmann Andersen; Lars Iversen; Jürgen C. Becker; Niels Ødum

doi:10.1016/j.jid.2018.03.1526

SATB1 in malignant T cells

Simon Mayland Fredholm, Andreas Willerslev-Olsen, Özcan Met, Linda Kubat, Maria Gluud, Sarah L. Mathiasen, Christina Friese, Edda Blümel, David Leander Petersen, Tengpeng Hu, Claudia Nastasi, Lise M. Lindahl, Terkild Brink Buus, Thorbjørn Frej Krejsgaard, Mariusz A. Wasik, Katharina Luise Maria Kopp, Sergei B. Koralov, Jenny L. Persson, Charlotte Menne Bonefeld, Carsten GeislerAnders Woetmann Andersen, Lars Iversen, Jürgen C. Becker, Niels Ødum

Department of Immunology and Microbiology

26 Citations (Scopus)

Abstract

Deficient expression of SATB1 hampers thymocyte development and results in inept T-cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides, the most frequent variant of cutaneous T-cell lymphoma. Here, we report on a disease stage-associated decrease of SATB1 expression and an inverse expression of STAT5 and SATB1 in situ. STAT5 inhibited SATB1 expression through induction of microRNA-155. Decreased SATB1 expression triggered enhanced expression of IL-5 and IL-9 (but not IL-6 and IL-32), whereas increased SATB1 expression had the opposite effect, indicating that the microRNA-155 target SATB1 is a repressor of IL-5 and IL-9 in malignant T cells. In accordance, inhibition of STAT5 and its upstream activator JAK3 triggered increased SATB1 expression and a concomitant suppression of IL-5 and IL-9 expression in malignant T cells. In conclusion, we provide a mechanistic link between the proto-oncogenic JAK3/STAT5/microRNA-155 pathway, SATB1, and cytokines linked to CTCL severity and progression, indicating that SATB1 dysregulation is involved in cutaneous T-cell lymphoma pathogenesis.

Original language	English
Journal	The Journal of Investigative Dermatology
Volume	138
Issue number	8
Pages (from-to)	1805-1815
Number of pages	11
ISSN	0022-202X
DOIs	https://doi.org/10.1016/j.jid.2018.03.1526
Publication status	Published - Aug 2018

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10.1016/j.jid.2018.03.1526

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Fredholm, S. M., Willerslev-Olsen, A., Met, Ö., Kubat, L., Gluud, M., Mathiasen, S. L., Friese, C., Blümel, E., Petersen, D. L., Hu, T., Nastasi, C., Lindahl, L. M., Buus, T. B., Krejsgaard, T. F., Wasik, M. A., Kopp, K. L. M., Koralov, S. B., Persson, J. L., Bonefeld, C. M., ... Ødum, N. (2018). SATB1 in malignant T cells. The Journal of Investigative Dermatology, 138(8), 1805-1815. https://doi.org/10.1016/j.jid.2018.03.1526

Fredholm, SM, Willerslev-Olsen, A, Met, Ö, Kubat, L, Gluud, M, Mathiasen, SL, Friese, C, Blümel, E, Petersen, DL, Hu, T, Nastasi, C, Lindahl, LM, Buus, TB, Krejsgaard, TF, Wasik, MA, Kopp, KLM, Koralov, SB, Persson, JL, Bonefeld, CM, Geisler, C , Andersen, AW, Iversen, L, Becker, JC & Ødum, N 2018, 'SATB1 in malignant T cells', The Journal of Investigative Dermatology, vol. 138, no. 8, pp. 1805-1815. https://doi.org/10.1016/j.jid.2018.03.1526

@article{e025cf5bb3ed4bffa605d8c1651eb730,

title = "SATB1 in malignant T cells",

abstract = "Deficient expression of SATB1 hampers thymocyte development and results in inept T-cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides, the most frequent variant of cutaneous T-cell lymphoma. Here, we report on a disease stage-associated decrease of SATB1 expression and an inverse expression of STAT5 and SATB1 in situ. STAT5 inhibited SATB1 expression through induction of microRNA-155. Decreased SATB1 expression triggered enhanced expression of IL-5 and IL-9 (but not IL-6 and IL-32), whereas increased SATB1 expression had the opposite effect, indicating that the microRNA-155 target SATB1 is a repressor of IL-5 and IL-9 in malignant T cells. In accordance, inhibition of STAT5 and its upstream activator JAK3 triggered increased SATB1 expression and a concomitant suppression of IL-5 and IL-9 expression in malignant T cells. In conclusion, we provide a mechanistic link between the proto-oncogenic JAK3/STAT5/microRNA-155 pathway, SATB1, and cytokines linked to CTCL severity and progression, indicating that SATB1 dysregulation is involved in cutaneous T-cell lymphoma pathogenesis.",

author = "Fredholm, {Simon Mayland} and Andreas Willerslev-Olsen and {\"O}zcan Met and Linda Kubat and Maria Gluud and Mathiasen, {Sarah L.} and Christina Friese and Edda Bl{\"u}mel and Petersen, {David Leander} and Tengpeng Hu and Claudia Nastasi and Lindahl, {Lise M.} and Buus, {Terkild Brink} and Krejsgaard, {Thorbj{\o}rn Frej} and Wasik, {Mariusz A.} and Kopp, {Katharina Luise Maria} and Koralov, {Sergei B.} and Persson, {Jenny L.} and Bonefeld, {Charlotte Menne} and Carsten Geisler and Andersen, {Anders Woetmann} and Lars Iversen and Becker, {J{\"u}rgen C.} and Niels {\O}dum",

year = "2018",

month = aug,

doi = "10.1016/j.jid.2018.03.1526",

language = "English",

volume = "138",

pages = "1805--1815",

journal = "The Journal of Investigative Dermatology",

issn = "0022-202X",

publisher = "nature publishing group",

number = "8",

}

TY - JOUR

T1 - SATB1 in malignant T cells

AU - Fredholm, Simon Mayland

AU - Willerslev-Olsen, Andreas

AU - Met, Özcan

AU - Kubat, Linda

AU - Gluud, Maria

AU - Mathiasen, Sarah L.

AU - Friese, Christina

AU - Blümel, Edda

AU - Petersen, David Leander

AU - Hu, Tengpeng

AU - Nastasi, Claudia

AU - Lindahl, Lise M.

AU - Buus, Terkild Brink

AU - Krejsgaard, Thorbjørn Frej

AU - Wasik, Mariusz A.

AU - Kopp, Katharina Luise Maria

AU - Koralov, Sergei B.

AU - Persson, Jenny L.

AU - Bonefeld, Charlotte Menne

AU - Geisler, Carsten

AU - Andersen, Anders Woetmann

AU - Iversen, Lars

AU - Becker, Jürgen C.

AU - Ødum, Niels

PY - 2018/8

Y1 - 2018/8

N2 - Deficient expression of SATB1 hampers thymocyte development and results in inept T-cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides, the most frequent variant of cutaneous T-cell lymphoma. Here, we report on a disease stage-associated decrease of SATB1 expression and an inverse expression of STAT5 and SATB1 in situ. STAT5 inhibited SATB1 expression through induction of microRNA-155. Decreased SATB1 expression triggered enhanced expression of IL-5 and IL-9 (but not IL-6 and IL-32), whereas increased SATB1 expression had the opposite effect, indicating that the microRNA-155 target SATB1 is a repressor of IL-5 and IL-9 in malignant T cells. In accordance, inhibition of STAT5 and its upstream activator JAK3 triggered increased SATB1 expression and a concomitant suppression of IL-5 and IL-9 expression in malignant T cells. In conclusion, we provide a mechanistic link between the proto-oncogenic JAK3/STAT5/microRNA-155 pathway, SATB1, and cytokines linked to CTCL severity and progression, indicating that SATB1 dysregulation is involved in cutaneous T-cell lymphoma pathogenesis.

AB - Deficient expression of SATB1 hampers thymocyte development and results in inept T-cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides, the most frequent variant of cutaneous T-cell lymphoma. Here, we report on a disease stage-associated decrease of SATB1 expression and an inverse expression of STAT5 and SATB1 in situ. STAT5 inhibited SATB1 expression through induction of microRNA-155. Decreased SATB1 expression triggered enhanced expression of IL-5 and IL-9 (but not IL-6 and IL-32), whereas increased SATB1 expression had the opposite effect, indicating that the microRNA-155 target SATB1 is a repressor of IL-5 and IL-9 in malignant T cells. In accordance, inhibition of STAT5 and its upstream activator JAK3 triggered increased SATB1 expression and a concomitant suppression of IL-5 and IL-9 expression in malignant T cells. In conclusion, we provide a mechanistic link between the proto-oncogenic JAK3/STAT5/microRNA-155 pathway, SATB1, and cytokines linked to CTCL severity and progression, indicating that SATB1 dysregulation is involved in cutaneous T-cell lymphoma pathogenesis.

U2 - 10.1016/j.jid.2018.03.1526

DO - 10.1016/j.jid.2018.03.1526

M3 - Journal article

C2 - 29751003

SN - 0022-202X

VL - 138

SP - 1805

EP - 1815

JO - The Journal of Investigative Dermatology

JF - The Journal of Investigative Dermatology

IS - 8

ER -

SATB1 in malignant T cells

Abstract

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