Abstract
CD45 is a protein tyrosine phosphatase, which is well-known for regulating antigen receptor signalling in T
and 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-induced
proliferation in lymphocytes. Consequently, CD45 dysregulation could be implicated in aberrant Jak/Stat activation and
proliferation in lymphoproliferative diseases. Despite high expression of the CD45 ligand, Galectin-1, in skin lesions from
cutaneous T-cell lymphoma (CTCL), the malignant T cells exhibit constitutive activation of the Jak3/Stat3 signalling
pathway and uncontrolled proliferation. We show that CD45 expression is down-regulated on malignant T cells when
compared to non-malignant T cells established from CTCL skin lesions. Moreover, CD45 cross-linking does not suppress
the constitutive activation of Stat3 in the malignant T cells and there is no correlation between the level of activated Stat3
and the level of CD45 expression on the malignant T cells. Furthermore, in contrast to non-malignant T cells, the
malignant T cells are protected against CD45-mediated inhibition of proliferation. In conclusion, our data suggest that
CD45 dysregulation might play a role in the aberrant proliferation and Jak3/Stat3 activation in CTCL.
and 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-induced
proliferation in lymphocytes. Consequently, CD45 dysregulation could be implicated in aberrant Jak/Stat activation and
proliferation in lymphoproliferative diseases. Despite high expression of the CD45 ligand, Galectin-1, in skin lesions from
cutaneous T-cell lymphoma (CTCL), the malignant T cells exhibit constitutive activation of the Jak3/Stat3 signalling
pathway and uncontrolled proliferation. We show that CD45 expression is down-regulated on malignant T cells when
compared to non-malignant T cells established from CTCL skin lesions. Moreover, CD45 cross-linking does not suppress
the constitutive activation of Stat3 in the malignant T cells and there is no correlation between the level of activated Stat3
and the level of CD45 expression on the malignant T cells. Furthermore, in contrast to non-malignant T cells, the
malignant T cells are protected against CD45-mediated inhibition of proliferation. In conclusion, our data suggest that
CD45 dysregulation might play a role in the aberrant proliferation and Jak3/Stat3 activation in CTCL.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | The Open Leukemia Journal |
| Vol/bind | 3 |
| Sider (fra-til) | 9-15 |
| Status | Udgivet - 2010 |