Progress in chronic graft-versus-host disease

255 PRF deficiency occurs not only with allelic variants characterized by mutations in the coding region of the gene. McIlroy et al. reported that the occurrence of a C/T polymorphism at position-398 of the proximal promoter region of the PRF1 gene was associated with decreased quantities of PRF in CTLs in HIV infected patients. A decrease of about 50% of control PRF levels was observed in heterozygous patients but no patients homozygous for-398T/T mutations were studied. In this issue of the Revista Brasileira de Hematologia e Hemoterapia, Garcia et al. (6) present an analysis of the frequency of the C398T polymorphism in a cohort of 62 patients with hematological cancers that had no allelic disequilibrium when compared to control populations matched by inferred ascendency. However, they describe an excess of the C398T polymorphism in the patients taken as whole group compared with the controls. This discrepancy could be attributed to the small number of patients studied or to the criteria used to define the control population. It is worth mentioning that all patients, except for one, were heterozygous (C398T). The only homozygous patient has myelodysplastic syndrome, but unfortunately the corresponding clinical and epidemiological data were not included in the paper. Overall, the paper raises a number of important questions related to the role of PRF in hematological cancer and some points should be addressed in future studies: 1. Is the level of PRF reduced in the cancer patients studied as observed in HIV infected patients? 2. Is the CTL response of the lymphocytes of patients with the allelic variants normal when compared to patients with wild type and normal individuals? 3. What is the prevalence of the coding allelic variants in this group of patients? To clarify these important points it is necessary to increase the population enrolled and perform the entire PRF1 gene sequencing of patients and matched controls. A multicenter study would be welcome. 2. Lichtenheld MG, Podack ER. Structure of the human perforin gene. A simple gene organization with interesting potential regulatory sequences. Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice. I. Temperature sensitivity of human perforin mutants unmasks subtotal loss of cytotoxicity, delayed FHL, and a predisposition to cancer. al. Polymorphism in the proximal promoter region of the perforin gene and its impact on the course of HIV infection. The National Institute of Health (NIH) consensus conference on criteria …