Acute lymphoblastic leukemia (ALL) is a malignant lymphoid cells proliferation at early stage of differentiation, it is primarily a disease of children under six years of age ; approximately 80-85% are of precursor B-cell phenotype.
With improvements in diagnosis and treatment, overall cure rate for children with ALL reached 85% in the developed world. Multiple recent studies indicate that genetic polymorphisms play an influential role in childhood ALL susceptibility, treatment response and prognosis.
The purine analog mercaptopurine is a key medication for the successful treatment of childhood ALL, Inosine triphosphate pyrophosphatase (ITPA) is one of several enzymes whose job is to cleanse the nucleotide pool. It catalyze the pyrophosphohydrolysis of 6-thioITP and methylthioITP and prevents the accumulation of such potentially toxic compounds. Therefore, the end result is that the ITPase enzyme acts to reduce the amount of active forms of the 6-MP drug present in human cells.
Characterization of ITPA deficiency by genotyping for the most common inactivating single-nucleotide polymorphisms can prospectively identify patients at higher risk of mercaptopurine toxicity which can subsequently influence the outcome of the patients.