SATB1 in Malignant T Cells

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

doi:10.1016/j.jid.2018.03.1526

SATB1 in Malignant T Cells

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

44 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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Fredholm, S., 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., Wasik, M. A., Kopp, K. L., 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, S, 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, T, Wasik, MA, Kopp, KL, Koralov, SB, Persson, JL, Bonefeld, CM, Geisler, C, Woetmann, A, 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

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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 = "Simon Fredholm 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 L} and Tengpeng Hu and Claudia Nastasi and Lindahl, {Lise M} and Buus, {Terkild B} and Thorbj{\o}rn Krejsgaard and Wasik, {Mariusz A} and Kopp, {Katharina L} and Koralov, {Sergei B} and Persson, {Jenny L} and Bonefeld, {Charlotte M} and Carsten Geisler and 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",

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TY - JOUR

T1 - SATB1 in Malignant T Cells

AU - Fredholm, Simon

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 L

AU - Hu, Tengpeng

AU - Nastasi, Claudia

AU - Lindahl, Lise M

AU - Buus, Terkild B

AU - Krejsgaard, Thorbjørn

AU - Wasik, Mariusz A

AU - Kopp, Katharina L

AU - Koralov, Sergei B

AU - Persson, Jenny L

AU - Bonefeld, Charlotte M

AU - Geisler, Carsten

AU - Woetmann, Anders

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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