Ordering Recommendation

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

Mnemonic
TPMT2
Methodology

Polymerase Chain Reaction/Fluorescence Monitoring

Performed

Varies

Reported

5-10 days

New York DOH Approval Status
This test is New York DOH approved.
Specimen Required
Patient Preparation
Collect

Whole Blood: Lavender (EDTA), Pink (K2EDTA), or Yellow (ACD Solution A or B).
Saliva:
Collection Device by DNA Genotek (OCD-100, ARUP Supply #49295) available online through eSupply using ARUP Connect™ or by contacting ARUP Client Services at (800) 522-2787.

Specimen Preparation

Transport 3 mL whole blood. (Min: 1 mL) OR Transport the Saliva Collection Device.

Storage/Transport Temperature

Whole Blood: Refrigerated.
Saliva: Room temperature.

Unacceptable Conditions

Plasma or serum. Specimens collected in sodium heparin or lithium heparin.

Remarks
Stability

Whole Blood: Ambient: 72 hours; Refrigerated: 1 week; Frozen: 1 month
Saliva:
Ambient: 2 weeks; Refrigerated: Unacceptable; Frozen: Unacceptable

Reference Interval

By report

Interpretive Data

Background Information for TPMT and NUDT15:
Characteristics:
Thiopurine drug therapy is used for autoimmune diseases, inflammatory bowel disease, acute lymphoblastic leukemia, and to prevent rejection after solid organ transplant. The inactivation of thiopurine drugs is catalyzed in part by thiopurine methyltrasferase (TPMT) and nudix hydrolase 15 (NUDT15). Variants in the TPMT and/or NUDT15 genes are associated with an accumulation of cytotoxic metabolites leading to increased risk of drug-related toxicity with standard doses of thiopurine drugs. These effects on thiopurine catabolism can be additive.
Inheritance:
Autosomal codominant.
Cause:
TPMT and NUDT15 variants affect enzyme expression or activity.
Variants Tested:
See the Additional Technical Information document.
Clinical Sensitivity:
95 percent.
Methodology:
Polymerase chain reaction (PCR) and fluorescence monitoring.
Analytical Sensitivity and Specificity:
99 percent.
Limitations:
Only the targeted TPMT and NUDT15 variants will be detected by this test. Because the complex TPMT*3A allele contains the variants found in the *3B and *3C alleles, this test cannot distinguish the 3A/Negative genotype (intermediate enzyme activity) from the rare *3B/*3C genotype (no or low enzyme activity). Genotyping may reflect donor status in patients who have received allogenic stem cell or bone marrow transplants within 2 weeks of specimen collection. Actual enzyme activity and expression and risk for adverse reactions to thiopurines may be affected by additional genetic and non-genetic factors not evaluated by this test. Diagnostic errors can occur due to rare sequence variations. Genotyping does not replace the need for therapeutic drug monitoring and clinical observation. 

Please note the information contained in this report does not contain medication recommendations, and should not be interpreted as recommending any specific medications. Any dosage adjustments or other changes to medications should be evaluated in consultation with a medical provider.

Compliance Category

Laboratory Developed Test (LDT)

Note

Whole blood is the preferred specimen. Saliva samples that yield inadequate DNA quality and/or quantity will be reported as inconclusive if test performance does not meet laboratory-determined criteria for reporting.

Hotline History
N/A
CPT Codes

81335; 81306

Components
Component Test Code* Component Chart Name LOINC
3001536 TPMT2 Specimen 31208-2
3001537 TPMT Genotype 41048-0
3001538 NUDT15 Genotype 93194-9
3001539 TPMT2 Interpretation 50398-7
* Component test codes cannot be used to order tests. The information provided here is not sufficient for interface builds; for a complete test mix, please click the sidebar link to access the Interface Map.
Aliases
  • 6-mercaptopurine
  • 6-MP
  • 6-TG
  • 6-thioguanine
  • AZA toxicity
  • Azathioprine
  • nucleoside diphosphate linked moiety X
  • nudix
  • NUDT15 mutation
  • S-adenosyl-L-methionine genotype
  • Thioguanine
  • Thiopurine
  • Thiopurine S-methyltransferase genotype
  • TPMT genetics
  • TPMT mutation
TPMT and NUDT15