Development of Lymphoma in Autoimmune Lymphoproliferative Syndrome (ALPS) and its Relationship to Fas Gene Mutations

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摘要：

Autoimmune Lymphoproliferative Syndrome (ALPS) is generally the result of a mutation in genes associated with apoptosis, like Fas, Fas ligand, Casp 8 and Casp 10. As a result, the normal homeostasis of T- and B-lymphocytes is disturbed and a proliferation of polyclonal T lymphocytes occurs. This leads to hepatosplenomegaly and lymphadenopathy and in most patients also to autoimmune phenomena like anemia and thrombocytopenia. The proliferating T cells are TCR± and/or TCR positive but lack both CD4 and CD8. Hence they are termed double negative (DN) T cells. In addition, there is an increase of CD5 positive B cells. Individuals with germline mutations in the Fas gene have a high risk to develop non Hodgkin lymphomas ( 14) as well as Hodgkin lymphomas ( 51), in particular NLP Hodgkin lymphoma. Somatic mutations of Fas are frequently acquired during the normal germinal center reaction. Non Hodgkin lymphomas carry somatic mutations of the Fas gene in 11% and of the Casp 10 gene in 14.5% of the patients. In Hodgkin lymphomas, Fas mutations can be demonstrated in Reed-Sternberg cells in 10 20% of the patients. These data implicate a role for Fas-mediated apoptosis in preventing lymphomas. Inherited defects in receptor-mediated lymphocyte apoptosis represent a risk factor for lymphomas and somatic mutations of these genes may also play a role in the development and/or progression of lymphomas.

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关键词：

Autoimmune Lymphoproliferative Syndrome (ALPS), Fas, Caspase 10, non Hodgkin lymphoma, NLP Hodgkin lymphoma, TCR gamma delta

DOI：

10.1080/10428190310001593166

被引量：

380

年份：

2004