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Biological and Clinical Implications of Exon 8 P53 (R282W) Gene Mutation in Relation to Development and Progression of Chronic Myeloid Leukaemia Patients in India Population

Rashid Mir, Mariyam Zuberi, Imtiyaz Ahmad, Jamsheed Javid, Prasant Yadav, Shazia Farooq, M Masroor, Sameer Guru, Sheikh Shanawaz, Ajaz Ah Bhat, Tanvir S Khatlani, Sunita Jetly, P C Ray, Naresh Gupta and Alpana Saxena

Background: TP53, located on chromosome 17p13, is one of the most mutated genes affecting many types of human cancers .To establish an association between the incidence of exon 8 p53 (R282W) gene and progression of the disease in CML and also to correlate the presence of mutation with the clinicopathological features of the disease. Methods: p53 status was investigated by studying mutations in the p53 gene at exon 8 region after confirming the diagnosis by BCR-ABL. 100 CML samples were analyzed using the Allele-Specific Oligonucleotide PCR assay. Mutations occurred in 58% of the cases in exon 8 codon 282 region of the p53 gene. C : T transitions occurred at a high frequency with a statistically significant result (p=0.03). Results: Of the 100 clinically confirmed specimens, 58% tested positive for the mutation. Also, the mutation was found to be higher in the progressed stages (88.2% in accelerated phase and 60.0% in blast crisis) of CML compared to the chronic stage (35.2%). A statistically significant association (p=0.001) was found between the occurrence of p53 R282W mutation and the clinical phase of CML with chronic, accelerated and blast crisis phases. The mutation was detected in a vast majority (88.2%) of patients in the accelerated and the blast crisis phase (60.0%) indicating that this mutation might play a critical role in predicting the progression of disease in CML. Clinicopathological correlation with TLC, platelet count and the haematological response elicited a significant association with patients harboring the mutation with (p=0.01), (p=0.001) and (p=0.01) respectively. Conclusion: Our study suggests that p53 mutations in the exon 8 region might have a strong influence on disease progression and poor response of imatiib (Tyrosine kinase inhibitor) in CML patients.