Acute lymphoblastic leukemia treatment thiopurines

Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurine dmgs, such as 6-mercaptopurine (6-MP), 6-thioguanine and azathioprine, to inactive metabolites [29-32]. Thiopurines form part of the routine treatment for patients with acute lymphoblastic leukemia, rheumatoid arthritis, and autoimmune diseases such as SLE and Crohn s disease, and are used as an immunosuppressant following organ transplantation. 

Deficiency of thiopurine S-methyl transferase (TPMT) is another phenotype that exhibits inter-ethnic differences in frequency. TPMT is an enzyme that catalyzes methylation of therapeutic agents used in the treatment of acute lymphoblastic leukemia, rheumatoid arthritis, and autoimmune/inflammatory diseases, as well as in organ transplantation. Patients who have TPMT deficiency experience less efficient methylation and are at greater risk of fatal toxicity when treated with standard doses of fhiopurines. TPMT phenotype is defined by erythrocyte 6-mercapto-purine methylation. African American populations exhibit a 20% lower erythrocyte TPMT than Caucasian Americans, and persons of Chinese descent tend to exhibit greater activity than either of these other American subpopulations. 

Stanulla, M., Schaeffeler, E., Hohr, T., et al. (2005) Thiopurine methyltransferase (TPMT) genotype and early treatment response to mercaptopurine in childhood acute lymphoblastic leukemia JAMA. 293, 1485-1489. 

Thiopurines in the Treatment of Childhood Acute Lymphoblastic Leukemia and Genetic Variants of the Thiopurine S-Methyltransferase Gene... 

The thiopurines 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are essential components of treatment protocols for childhood acute lymphoblastic leukemia... 

THIOPURINES IN THE TREATMENT OF CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA... 

Stanulla M, Schaeffeler E, Moricke A et al. Thiopurine methyltransferase genotype is not a risk factor for secondary malignant neoplasias after treatment for childhood acute lymphoblastic leukemia on Berlin FrankfurtMunster protocols. Blood 2006 108 48a. 

Lennard L, Lilleyman JS. Variable mercaptopurine metabolism and treatment outcome in childhood lymphoblastic leukemia. J Clin Oncol 1989 7 1816-1823. Erratum itv.JClin Oncol 1990 8 567. Lennard L, Lewis IJ, Michelagnoli M et al. Thiopurine methyltransferase deficiency in childhood lymphoblastic leukaemia 6-mercaptopurine dosage strategies. MedPediatr Oncol 1997 29 252-255. Lennard L, Van Loon JA, Weinshilboum RM. Pharmaeogenetics of acute azathioprine toxicity relationship to thiopurine methyltransferase genetic polymorphism. Clin Pharmacol Ther 1989 46 149-154. 

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