Certain genetic variations within the TPMT gene can lead to decreased or absent TPMT enzyme activity, and individuals who are homozygous or heterozygous for these types of genetic variations may have increased levels of TGN metabolites and an increased risk of severe bone marrow suppression (myelosuppression) when receiving mercaptopurine. In many ethnicities, TPMT polymorphisms that result in decreased or absent TPMT activity occur with a frequency of approximately 5%, meaning that about 0.25% of people are homozygous for these variants. However, an assay of TPMT activity in red blood cells or a TPMT genetic test can identify people with reduced TPMT activity, allowing for the adjustment of mercaptopurine dose or avoidance of the drug entirely. The FDA-approved drug label for mercaptopurine recommends testing for TPMT activity to identify people at risk for myelotoxicity. Testing for TPMT activity is an example of pharmacogenetics being translated into routine clinical care. History
6-MP was discovered by Nobel Prize winning scientists Gertrude B. Elion and George H. Hitchings at Burroughs Wellcome in Tuckahoe, New York, and was clinically developed in collaboration with investigators at Memorial Hospital (now Memorial Sloan Kettering Cancer Center in New York City). The collaboration was initiated by Cornelius P. Rhoads who had run chemical weapons programs for the US army and had been involved in the work that led to the discovery that nitrogen mustards could potentially be used as cancer drugs, and had become the director of Memorial in 1948. See also
Azathioprine
Tioguanine

References
Further reading
Dean L (2012). "Mercaptopurine Therapy and TPMT Genotype".
thiopurine nucleotides can help to optimize the efficacy and safety. Clinically, most hospitals resort to on-exchange LC-MS (liquid chromatography - mass spectrometry) but the newly developed approach of porous graphitic carbon based chromatography hyphenated with mass spectrometry appears superior with respect to patient care in this respect.Symptoms of allergic reaction to mercaptopurine include rash, itching, swelling, dizziness, trouble breathing, and inflammation of the pancreas. In some cases, mercaptopurine may suppress the production of blood cells, both white blood cells and red blood cells. It may be toxic to bone marrow. Quarterly blood counts are necessary for people on mercaptopurine. People should stop taking the medication at least temporarily while considering alternate treatment if there is an unexplained, abnormally large drop in white blood cell count, or any other blood count. Toxicity of mercaptopurine can be linked to genetic polymorphisms in thiopurine S-methyltransferase (TPMT), nudix hydrolase 15 (NUDT15), and inosine triphosphate pyrophosphatase (ITPA). People with specific allele variants will require dose adjustments, especially for those with homozygous variant genotypes. Large differences of TPMT and NUDT15 among ethnicities in terms of variant allele frequency should be taken into consideration in clinical practice. Caucasian people with a variant allele of the ITPA gene, experience higher rates of febrile neuropenia than people of other ethnic groups, due to differences in allelic frequencies among ethnicities. Precautions
Mercaptopurine can lower the bodys ability to fight off infection. Those taking it should get permission from a doctor to receive immunizations and vaccinations.