Malignant T cells exhibit CD45 resistant Stat 3 activation and proliferation in cutaneous T cell lymphoma.

TY - JOUR

T1 - Malignant T cells exhibit CD45 resistant Stat 3 activation and proliferation in cutaneous T cell lymphoma.

AU - Krejsgaard, T

AU - Helvad, Rikke

AU - Ralfkiær, Elisabeth

AU - Astvad, K

AU - Grønbæk, K

AU - Eriksen, KW

AU - Geisler, C

AU - Kopp, Katharina Luise Maria

AU - Zhang, Q

AU - Ødum, Niels

AU - Andersen, Anders Woetmann

AU - Katharina, K

AU - Wasik, MA

AU - Odum, N

AU - Woetmann, A

PY - 2010

Y1 - 2010

N2 - CD45 is a protein tyrosine phosphatase, which is well-known for regulating antigen receptor signalling in Tand B cells via its effect on Src kinases. It has recently been shown that CD45 can also dephosphorylate Janus kinases(Jaks) and thereby regulate Signal transducer and activator of transcription (Stat) activation and cytokine-inducedproliferation in lymphocytes. Consequently, CD45 dysregulation could be implicated in aberrant Jak/Stat activation andproliferation in lymphoproliferative diseases. Despite high expression of the CD45 ligand, Galectin-1, in skin lesions fromcutaneous T-cell lymphoma (CTCL), the malignant T cells exhibit constitutive activation of the Jak3/Stat3 signallingpathway and uncontrolled proliferation. We show that CD45 expression is down-regulated on malignant T cells whencompared to non-malignant T cells established from CTCL skin lesions. Moreover, CD45 cross-linking does not suppressthe constitutive activation of Stat3 in the malignant T cells and there is no correlation between the level of activated Stat3and the level of CD45 expression on the malignant T cells. Furthermore, in contrast to non-malignant T cells, themalignant T cells are protected against CD45-mediated inhibition of proliferation. In conclusion, our data suggest thatCD45 dysregulation might play a role in the aberrant proliferation and Jak3/Stat3 activation in CTCL

AB - CD45 is a protein tyrosine phosphatase, which is well-known for regulating antigen receptor signalling in Tand B cells via its effect on Src kinases. It has recently been shown that CD45 can also dephosphorylate Janus kinases(Jaks) and thereby regulate Signal transducer and activator of transcription (Stat) activation and cytokine-inducedproliferation in lymphocytes. Consequently, CD45 dysregulation could be implicated in aberrant Jak/Stat activation andproliferation in lymphoproliferative diseases. Despite high expression of the CD45 ligand, Galectin-1, in skin lesions fromcutaneous T-cell lymphoma (CTCL), the malignant T cells exhibit constitutive activation of the Jak3/Stat3 signallingpathway and uncontrolled proliferation. We show that CD45 expression is down-regulated on malignant T cells whencompared to non-malignant T cells established from CTCL skin lesions. Moreover, CD45 cross-linking does not suppressthe constitutive activation of Stat3 in the malignant T cells and there is no correlation between the level of activated Stat3and the level of CD45 expression on the malignant T cells. Furthermore, in contrast to non-malignant T cells, themalignant T cells are protected against CD45-mediated inhibition of proliferation. In conclusion, our data suggest thatCD45 dysregulation might play a role in the aberrant proliferation and Jak3/Stat3 activation in CTCL

U2 - 10.2174/1876816401003010009

DO - 10.2174/1876816401003010009

M3 - Journal article

SN - 1876-8164

VL - 3

SP - 9

EP - 15

JO - The Open Leukemia Journal

JF - The Open Leukemia Journal

ER -