Lnk constrains myeloproliferative diseases in mice

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Lnk constrains myeloproliferative diseases in mice.

Hematopoietic stem and progenitor cell (HSPC) expansion is regulated by intrinsic signaling pathways activated by cytokines. The intracellular kinase JAK2 plays an essential role in cytokine signaling, and activating mutations in JAK2 are found in a number of hematologic malignancies. We previously demonstrated that lymphocyte adaptor protein (Lnk, also known as Sh2b3) binds JAK2 and attenuates...

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The Polymorphisms in LNK Gene Correlated to the Clinical Type of Myeloproliferative Neoplasms

OBJECTIVE LNK is an adapter protein negatively regulating the JAK/STAT cell signaling pathway. In this study, we observed the correlation between variation in LNK gene and the clinical type of myeloproliferative neoplasms (MPN). METHODS A total of 285 MPN cases were recruited, including essential thrombocythemia (ET) 154 cases, polycythemia vera (PV) 76 cases, primary myelofibrosis (PMF) 19 c...

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Platelets and thrombosis in myeloproliferative diseases.

The myeloproliferative disorders have been the "poor cousins" in the family of hematological malignancies for some time. Recently this field has advanced considerably with the description of a mutation in the JAK2 kinase detectable in the majority of patients and the publication of two landmark clinical trials--ECLAP and MRC PT1. But although both ECLAP and MRC PT1 inform clinical management an...

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Adaptor protein Lnk negatively regulates the mutant MPL, MPLW515L associated with myeloproliferative disorders.

Recently, activating myeloproliferative leukemia virus oncogene (MPL) mutations, MPLW515L/K, were described in myeloproliferative disorder (MPD) patients. MPLW515L leads to activation of downstream signaling pathways and cytokine-independent proliferation in hematopoietic cells. The adaptor protein Lnk is a negative regulator of several cytokine receptors, including MPL. We show that overexpres...

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ژورنال

عنوان ژورنال: Journal of Clinical Investigation

سال: 2010

ISSN: 0021-9738

DOI: 10.1172/jci42032