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201904151249411

TPMT-MAMAPCR real time

Quantification assay of Thiopurine Methyltransferase          cod. BM-007

 

Principle of the test: Detect abnormal TPMT enzyme activity due to genetics

Technology: MAMA PCR real time

Gene Target: TPMT 2, 3B, 3C

Specimen: DNA

Results: Haplotype set

Reporting Units: Arbitrary Units (AU)

Number of tests: 25 tests BM-007

Kit storage: -20°C

Necessary equipment: 7500 Real Time PCR System

Status: Ready to use

TPMT-MAMAPCR real time cod. BM-007

 

Quantification assay of Thiopurine Methyltransferase

 

·      TPMT-MAMAPCR real time Quantification complete kit 25 tests BM-007

 

Thiopurine drugs such as azathioprine (AZA), 6-mercaptopurine (6-MP), and 6-thioguanine (6-TG) are widely used in the treatment of acute lymphoblastic leukemia (ALL), autoimmune diseases, inflammatory bowel disease, and posttransplant organ rejection. Patients with abnormal thiopurine methyltransferase (TPMT) enzyme activity due to genetics and/or drug-drug interactions have an increased risk of toxicity when given thiopurines.

Recommended Use: Genotype test to assess risk, due to genetics, for severe myelosuppression with standard dosing of thiopurine drugs; individuals being considered for thiopurine therapy or who have had an adverse reaction to thiopurine therapy; patients with recent heterologous blood transfusion.

Can be performed irrespective of thiopurine therapy.

Limitations: only targeted TPMT allele variants will be detected by this panel; Diagnostic errors can occur due to rare sequence variations; Genotyping cannot distinguish between the *3A/negative and *3B/*3C genotypes; Genotyping does not replace the need for therapeutic drug monitoring or clinical observation; Genotyping in patients who have received allogenic stem cell/bone marrow transplant will reflect donor status.

We have established a MAMA PCR real time analysis for the detection of TPMT*2, *3B, and *3C without a sequencing step. In clinical practice, identification of TPMT polymorphisms can help prevent severe thiopurine-induced adverse effects, mainly myelotoxicity. Patients with acute lymphoblastic leukemia10, inflammatory bowel disease11, and dermatologic disorders12 are candidates for pharmacogenetically guided therapy with thiopurine. Moreover, Winter et al13 reported on the costeffectiveness of pretreatment screening for TPMT polymorphisms in patients with inflammatory bowel disease who are starting AZA therapy.

 

Reference

1.      Cheok MH, Lugthart S, Evans WE. Pharmacogenomics of acute leukemia. Annu Rev Pharmacol Toxicol. 2006;46:317–353.

2.      Kaskas BA, Louis E, Hindorf U, et al. Safe treatment of thiopurine S-methyltransferase deficient Crohn’s disease patients with azathioprine. Gut. 2003;52:140–142.

3.      Meggitt SJ, Gray JC, Reynolds NJ. Azathioprine dosed by thiopurine methyltransferase activity for moderate-tosevere atopic eczema: a double-blind, randomised controlled trial. Lancet. 2006;367:839– 846.

4.      Winter J, Walker A, Shapiro D, et al. Cost-effectiveness of thiopurine methyltransferase genotype screening in patients about to commence azathioprine therapy for treatment of inflammatory bowel disease. Aliment Pharm Ther. 2004;20:593–599.