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Shahid Ullah
Alex Tonks
Abdulsalam M Alruwaili
Hedib Alkoumi H Alrawili
Asifullah Khan
Ahmad Salem Alanazi
Amirah Sayah S Alkuwaykibi
Carlos Eliel Maya-Ramírez
Muhammad Arif Lodhi


TP53, Messense Mutation, Acute lymphocytic leukemia, Docking.


Acute lymphoblastic leukaemia (ALL) is a significant threat to global health. Tumour suppressor gene TP53 mutations are often associated with a more aggressive form of leukaemia and poorer prognoses. This study conducted whole-exome sequencing of leukaemia patients at various treatment stages, including early diagnosis, relapse, and remission. We identified a missense 72 Arg/Pro (rs1042522) homozygous and heterozygous variant along with indel novel intron variant 376-158delAAAAAAA and 993+409delT in TP53. This mutational profile may serve as a predictor of poor treatment success in the Pakistani Pathan (Pakhtun) Population. Theoretical study explores the virtual repurposing of the FDA-approved drugs as inhibitors against these mutant TP53 cancers. The crystal structure of the TP53 proteins was downloaded from Alpha fold database and PDB and subjected to virtual screening by the DrugRep web server while using an FDA-approved drugs library as a ligands database. Our study revealed that Duvelisib and Robinin herb are the top-ranked inhibitors of MUT TP53 as compared to the reference chemotherapy. Duvelisib exhibited a docking score of −10.6 kcal/mol while Robinin herb scored –10.4 kcal/mol. In conclusion the two drugs deserve further consideration as possible cancer treatment option.

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