Thiopurine S methyltranferase deficiency

A hereditary autosomal recessive condition that results in an increased sensitivity to 6-MERCAPTOPURINE due to mutations in thiopurine methyltransferase (TPMT gene) causing decreased enzyme activity. OMIM: 187680

Also Known As:

Networked: 63 relevant articles (3 outcomes, 4 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Acute Myeloid Leukemia (Acute Myelogenous Leukemia)
2.	Cardiotoxicity
3.	Febrile Neutropenia
4.	Crohn Disease (Crohn's Disease)
5.	Body Weight (Weight, Body)

Experts

1.	Barclay, Murray L: 4 articles (07/2015 - 01/2006)
2.	Arenas-Hernandez, Monica: 2 articles (01/2020 - 11/2012)
3.	Marinaki, Anthony M: 2 articles (01/2020 - 03/2004)
4.	Wong, Dennis R: 2 articles (12/2019 - 02/2017)
5.	Schuetz, John D: 2 articles (08/2017 - 07/2008)
6.	Roberts, Rebecca L: 2 articles (07/2015 - 10/2012)
7.	Oellerich, Michael: 2 articles (10/2012 - 12/2005)
8.	von Ahsen, Nicolas: 2 articles (10/2012 - 12/2005)
9.	Marinaki, A: 2 articles (06/2011 - 10/2002)
10.	Czaja, Albert J: 2 articles (05/2007 - 05/2006)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Thiopurine S methyltranferase deficiency:

1.	Azathioprine (Imuran)FDA LinkGeneric 09/01/2011 - "TPMT deficiency is associated with azathioprine (AZA)-induced myelosuppression (MS). " 05/01/2007 - "Screening for thiopurine methyltransferase deficiency does not predict azathioprine intolerance. " 10/01/2006 - "Two cases are presented that illustrate the very different outcomes that may occur with azathioprine in patients with TPMT deficiency, which affects 0.3-0.6% of caucasians. " 05/01/2006 - "Thiopurine methyltransferase deficiency has been associated with intolerance to azathioprine. " 09/01/1995 - "Thiopurine methyltransferase deficiency occurs at a frequency of one in 300 and is associated with profound myelosuppression after a short course of azathioprine. "
2.	2-mercaptopurineIBA 10/01/2012 - "To study the significance of TPMT deficiency in thiopurine metabolism and immunosuppressive activity in vitro, we established RNA interference-based TPMT knockdown (kd) in a Jurkat cell line. " 04/01/2014 - "The development of severe bone marrow toxicity, in patients taking standard doses of thiopurine drugs, is associated with TPMT deficiency whilst the TPMT heterozygote is at an increased risk of developing myelosuppression. " 06/01/2011 - "Adverse effects of thiopurine drugs occur in 15-28% of patients and the majority is not explained by thiopurine-S-methyltransferase deficiency. " 07/01/2008 - "Thiopurine S-methyltransferase deficiency is known to exacerbate thiopurine toxicity. " 10/01/2012 - "We conclude that TPMT kd cells are an appropriate in vitro model to investigate the significance of TPMT deficiency with thiopurine therapy and could be helpful in understanding possible clinical consequences of TPMT polymorphism."
3.	Mercaptopurine (6 Mercaptopurine)FDA LinkGeneric 10/01/1997 - "Thiopurine methyltransferase deficiency in childhood lymphoblastic leukaemia: 6-mercaptopurine dosage strategies." 11/01/1993 - "Congenital thiopurine methyltransferase deficiency and 6-mercaptopurine toxicity during treatment for acute lymphoblastic leukaemia." 01/01/2023 - "Although mercaptopurine-dose reduction reduces toxicity risk without compromising relapse rate in patients with TPMT deficiency, dosing recommendations for those with moderately reduced activity (intermediate metabolizer (IM)) are less clear and their clinical impacts have yet to be established. " 01/01/2019 - "Since patients with NUDT15 or TPMT deficiency suffer severe adverse drug reactions, star (*) allele-based haplotypes have been used to predict an optimal 6-mercaptopurine (6-MP) dosing. " 12/01/1991 - "This case demonstrates that thiopurine methyltransferase deficiency does not absolutely contraindicate mercaptopurine therapy, and it also provides insight into the mechanism of excessive toxic effects of mercaptopurine sometimes observed in children with acute lymphocytic leukemia."
4.	Methotrexate (Mexate)FDA LinkGeneric 01/01/1998 - "Pharmacokinetics, dose adjustments, and 6-mercaptopurine/methotrexate drug interactions in two patients with thiopurine methyltransferase deficiency." 10/01/2012 - "In this review we summarize what is known about TPMT deficiency and explore whether there is evidence to support a role of other genetic polymorphisms in predicting the response of CD patients to thiopurine drugs, methotrexate, and anti-tumor necrosis factor α (TNFα) therapy." 08/01/1997 - "We have learned, for example, the following: high-dose methotrexate is more effective than lower-dose methotrexate, especially for T-cell ALL; patients who need drastic adjustment of mercaptopurine dosage due to thiopurine S-methyltransferase deficiency can be prospectively identified; dexrazoxane (ICRF-187) could reduce anthracycline cardiotoxicity; granulocyte colony-stimulating factor can shorten hospital stays for febrile neutropenia after intensive remission induction therapy; and prolonged low-dose epipodophyllotoxin treatment may reduce the risk of therapy-induced acute myeloid leukemia without compromising treatment efficacy. "
5.	Dexrazoxane (Zinecard)FDA LinkGeneric 08/01/1997 - "We have learned, for example, the following: high-dose methotrexate is more effective than lower-dose methotrexate, especially for T-cell ALL; patients who need drastic adjustment of mercaptopurine dosage due to thiopurine S-methyltransferase deficiency can be prospectively identified; dexrazoxane (ICRF-187) could reduce anthracycline cardiotoxicity; granulocyte colony-stimulating factor can shorten hospital stays for febrile neutropenia after intensive remission induction therapy; and prolonged low-dose epipodophyllotoxin treatment may reduce the risk of therapy-induced acute myeloid leukemia without compromising treatment efficacy. "
6.	AnthracyclinesIBA 08/01/1997 - "We have learned, for example, the following: high-dose methotrexate is more effective than lower-dose methotrexate, especially for T-cell ALL; patients who need drastic adjustment of mercaptopurine dosage due to thiopurine S-methyltransferase deficiency can be prospectively identified; dexrazoxane (ICRF-187) could reduce anthracycline cardiotoxicity; granulocyte colony-stimulating factor can shorten hospital stays for febrile neutropenia after intensive remission induction therapy; and prolonged low-dose epipodophyllotoxin treatment may reduce the risk of therapy-induced acute myeloid leukemia without compromising treatment efficacy. "
7.	Granulocyte Colony-Stimulating Factor (G-CSF)IBA 08/01/1997 - "We have learned, for example, the following: high-dose methotrexate is more effective than lower-dose methotrexate, especially for T-cell ALL; patients who need drastic adjustment of mercaptopurine dosage due to thiopurine S-methyltransferase deficiency can be prospectively identified; dexrazoxane (ICRF-187) could reduce anthracycline cardiotoxicity; granulocyte colony-stimulating factor can shorten hospital stays for febrile neutropenia after intensive remission induction therapy; and prolonged low-dose epipodophyllotoxin treatment may reduce the risk of therapy-induced acute myeloid leukemia without compromising treatment efficacy. "
8.	Podophyllotoxin (Condylox)FDA LinkGeneric 08/01/1997 - "We have learned, for example, the following: high-dose methotrexate is more effective than lower-dose methotrexate, especially for T-cell ALL; patients who need drastic adjustment of mercaptopurine dosage due to thiopurine S-methyltransferase deficiency can be prospectively identified; dexrazoxane (ICRF-187) could reduce anthracycline cardiotoxicity; granulocyte colony-stimulating factor can shorten hospital stays for febrile neutropenia after intensive remission induction therapy; and prolonged low-dose epipodophyllotoxin treatment may reduce the risk of therapy-induced acute myeloid leukemia without compromising treatment efficacy. "
9.	Proteins (Proteins, Gene)FDA Link 10/24/2003 - "Biochemical studies have demonstrated that TPMT deficiency is primarily associated with increased degradation of the polymorphic proteins through an ubiquitylation and proteasomal-dependent pathway. " 10/01/1999 - "Thus, enhanced proteolysis of TPMT*3C protein in mammalian cells is in contrast to its stability in yeast, but consistent with TPMT-deficiency in humans. " 10/01/1999 - "However, unlike TPMT*2 and TPMT*3A, the catalytically active protein coded by TPMT*3C does not undergo enhanced proteolysis when heterologously expressed in yeast, making it unclear why this common mutant allele should be associated with inheritance of TPMT-deficiency. "
10.	Inosine TriphosphataseIBA 12/01/2005 - "Association of inosine triphosphatase 94C>A and thiopurine S-methyltransferase deficiency with adverse events and study drop-outs under azathioprine therapy in a prospective Crohn disease study."

Therapies and Procedures

1.	Therapeutics 04/15/2001 - "There is a significant (> six-fold) overrepresentation of TPMT deficiency or heterozygosity among patients developing dose-limiting hematopoietic toxicity from therapy containing thiopurines. " 10/01/2012 - "We conclude that TPMT kd cells are an appropriate in vitro model to investigate the significance of TPMT deficiency with thiopurine therapy and could be helpful in understanding possible clinical consequences of TPMT polymorphism." 02/01/2007 - "Pharmacogenetic screening for TPMT polymorphisms before commencing azathioprine therapy may help to prevent severe hematotoxicity in patients with TPMT deficiency." 01/01/2020 - "There is increasing evidence that testing for NUDT15 and TPMT deficiency in all populations prior to the start of thiopurine therapy is clinically useful and should be the first step in personalising thiopurine therapy." 01/01/2020 - "Testing for thiopurine methyltransferase (TPMT) deficiency directs a safe initial dose for therapy. "
2.	Remission Induction 08/01/1997 - "We have learned, for example, the following: high-dose methotrexate is more effective than lower-dose methotrexate, especially for T-cell ALL; patients who need drastic adjustment of mercaptopurine dosage due to thiopurine S-methyltransferase deficiency can be prospectively identified; dexrazoxane (ICRF-187) could reduce anthracycline cardiotoxicity; granulocyte colony-stimulating factor can shorten hospital stays for febrile neutropenia after intensive remission induction therapy; and prolonged low-dose epipodophyllotoxin treatment may reduce the risk of therapy-induced acute myeloid leukemia without compromising treatment efficacy. "
3.	Length of Stay 08/01/1997 - "We have learned, for example, the following: high-dose methotrexate is more effective than lower-dose methotrexate, especially for T-cell ALL; patients who need drastic adjustment of mercaptopurine dosage due to thiopurine S-methyltransferase deficiency can be prospectively identified; dexrazoxane (ICRF-187) could reduce anthracycline cardiotoxicity; granulocyte colony-stimulating factor can shorten hospital stays for febrile neutropenia after intensive remission induction therapy; and prolonged low-dose epipodophyllotoxin treatment may reduce the risk of therapy-induced acute myeloid leukemia without compromising treatment efficacy. "
4.	Drug Therapy (Chemotherapy) 02/01/2006 - "They were found to have the homozygous polymorphism for thiopurine methyltransferase deficiency and recovered after cessation of drug therapy. " 04/01/2018 - "Identification of patients with thiopurine S-methyltransferase (TPMT) deficiency prior to thiopurine drug therapy has become routine clinical practice worldwide. "
5.	Immunomodulation 10/01/2012 - "Currently, thiopurine S-methyltransferase (TPMT) deficiency is the only pharmacogenetic factor that is prospectively assessed before azathioprine or 6-mercaptopurine immunomodulation is commenced in patients with Crohn's disease (CD). "