When the brakes are lost: LNK dysfunction in mice, men, and myeloproliferative neoplasms
In: Therapeutic Advances in Hematology, Jg. 2 (2010-12-22), S. 11-19
Online
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Zugriff:
Aberrant JAK-STAT signaling is a hallmark of myeloproliferative neoplasms (MPNs). These hyperproliferative disorders are classically associated with activating mutations in tyrosine kinases such as JAK2 and the thrombopoietin (TPO) receptor MPL. Activation of JAK-STAT signaling and responses to JAK2 inhibitors have been observed in MPN patients lacking JAK2 or MPL mutations, suggesting that other regulatory elements in the JAK-STAT pathway are altered. However, the molecular basis for this observation has been unclear. Recently, the role of inhibitory regulators of JAK-STAT signaling in MPN pathogenesis has been increasingly recognized. LNK is an adaptor protein that forms a negative feedback loop by binding to MPL and JAK2 and inhibiting downstream STAT activation. Murine models indicate that loss of LNK function can promote the development of a MPN phenotype. Several recent studies have identified novel LNK mutations in MPNs, thus validating this notion in humans. These findings represent a novel genetic paradigm of loss of negative feedback regulation of JAK-STAT activation in MPNs and have implications for the future development of targeted therapies in MPNs.
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When the brakes are lost: LNK dysfunction in mice, men, and myeloproliferative neoplasms
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Autor/in / Beteiligte Person: | Oh, Stephen T. |
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Zeitschrift: | Therapeutic Advances in Hematology, Jg. 2 (2010-12-22), S. 11-19 |
Veröffentlichung: | SAGE Publications, 2010 |
Medientyp: | unknown |
ISSN: | 2040-6215 (print) ; 2040-6207 (print) |
DOI: | 10.1177/2040620710393391 |
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