LNK mutations and myeloproliferative disorders

The lymphocyte adaptor protein (LNK) is one of a family of adaptor proteins involved cell signalling and control of B cell populations. It has a critical role in regulation of signalling in hematopoiesis. Lnk negatively regulates cytokine initiated cell signalling and it functions as a negative regulator of the mutant protein in myeloproliferative neoplasms JAK2V617F. A number of mutations in LNK have been described in a variety of myeloproliferative neoplasms some of which have been demonstrated to cause increased cellular proliferation. The majority of mutations occur in exon 2. In a small number of cases idiopathic erythrocytosis with subnormal erythropoietin levels LNK mutations have been found which may account for the clinical phenotype. Thus investigation for LNK mutations should be considered in the investigation of idiopathic erythrocytosis and perhaps other myeloproliferative neoplasms.