| dc.description.abstract | The IRF-1 protein, a mammalian transcriptional factor encoded by a gene located in 5q23-q31, hasantioncogenic properties. Involved in regulation of differentiation and proliferation, IRF-1 acts as a tumorsuppressor gene and is inactivated by deletion of its one or more exons (exon skipping) in many hematologicalmalignancies, including acute myelocytic leukemia (AML) and myelodysplastic syndromes (MDS). DNAsamples, extracted from peripheral blood, taken from 50 Kashmiri AML subjects, were analysed using thepolymerase chain reaction and compared with examples of age and gender matched healthy controls from thesame population. Three different exon regions (2, 3 and 4) of the IRF-1 gene that were previously shown tobe prone to deletion were selected for amplification and analysis. Deletion was observed in 31(62%) out of 50AML patients (p=0.016). Exon 3 was most frequently deleted (58%), followed by exon 2 (28%), while exon 4was least affected (12%), providing insights into critical roles in leukemogenesis. The number of deleted exonswas variable, but single exon deletions were more frequent (30%). Of interest, IRF-1 gene deletions were notobserved in 19 (38%) patients. In our study, the frequency of deletions of these three exons was slightly higherthan in an Indian population (52%), but lower than in Sweden in Europe (95%). This study also explored theprevalence and clinical profile of IRF-1 deletions in AML patients. Adults had a significantly higher incidencethan children (p=0.0168) and IRF-1 deletions were associated with low Hb (p<0.0001), high TLC (p=0.0033)and a low platelet count (p=0.0076). | en_US |
