perforin gene A proportion of patients with lymphoma may harbor mutations of the

Abstract Perforin mutations have been demonstrated in a proportion of patients diagnosed with the familial form of hemophagocytic lymphohistiocytosis (HLH). In the present study, we evaluated whether some patients with lymphoma sharing clinical characteristics with HLH might harbor mutations of the perforin gene. We analysed 29 patients and we found that 4 patients, who developed either Hodgkin or non-Hodgkin lymphoma, had bi-allelic mutations of the perforin gene. One of these 4 patients, a 19-year-old female with T-cell lymphoma, had a brother, carrying the same mutations, who developed HLH. In 2 out of the 4 patients with bi-allelic mutations of the perforin gene, we evaluated perforin expression by flow-cytometry and natural killer (NK) activity, and both were found to be absent. Moreover, we documented the presence of mono-allelic mutations of the perforin gene in 4 more patients. One of these 4 latter patients also carried a mutation of the Fas gene. These data indicate that perforin deficiency, either alone or in combination with other mutations of genes involved in lymphocyte survival or functional activity, may be present in patients with lymphoma. These findings suggest that perforin plays a key role also in the mechanisms of immune-surveillance that prevent tumor growth and/or development.Abstract words: 200Text words: 2.971From bloodjournal.hematologylibrary.org by guest on June 12, 2013. For personal use only.