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Fig. 1 | BMC Cancer

Fig. 1

From: Thiopurine Enhanced ALL Maintenance (TEAM): study protocol for a randomized study to evaluate the improvement in disease-free survival by adding very low dose 6-thioguanine to 6-mercaptopurine/methotrexate-based maintenance therapy in pediatric and adult patients (0–45 years) with newly diagnosed B-cell precursor or T-cell acute lymphoblastic leukemia treated according to the intermediate risk-high group of the ALLTogether1 protocol

Fig. 1

Intracellular metabolism of thiopurines and methotrexate. The tiopurines 6-mercaptopurine (6MP) and 6-thioguanine (6TG) are converted to thiguanine nucleotides (TGN) through sequential intracellular enzymatical steps. TGN are then incorporated into DNA (DNA-TG). The enzyme thiopurine methyl transferase (TPMT) creates methylated 6MP metabolites, which are associated with hepatotoxicity. Methotrexate (MTX) and some of the methylated 6MP metabolites inhibit purine de novo synthesis, thereby enhancing incorporation of TGN into DNA. Thus, DNA-TG is a downstream metabolite that integrates all upstream thiopurine and MTX metabolites

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BMC Cancer

ISSN: 1471-2407

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