title: Thiopurine methyltransferase genetics is not a major risk factor for secondary malignant neoplasms after treatment of childhood acute lymphoblastic leukemia on Berlin-Frankfurt-Münster protocols.
abstract: Thiopurine methyltransferase (TPMT)is involved in the metabolism of thiopurines such as 6-mercaptopurine and 6-thioguanine. TPMT activity is significantly altered by genetics, and heterozygous and even more homozygous variant people reveal substiantially decreased TPMT activity. Treatment for childhood acute lymphoblastic leukemia (ALL) regularly includes the use of thiopurine drugs. Importantly, childhood ALL patients with low TPMT activity have been considered to be at increased risk of developing therapy-associated acute myeloid leukemia and brain tumors. In the present study, we genotyped 105 of 129 patients who developed a secondary malignant neoplasm after ALL treatment on 7 consecutive German Berlin-Frankfurt-Münster trials for all functionally relevant TPMT variants. Frequencies of TPMT variants were similarly distributed in secondary malignant neoplasm patients and the overall ALL patient population of 814 patients. Thus, TPMT does not play a major role in the etiology of secondary malignant neoplasm after treatment for childhood ALL, according to Berlin-Frankfurt-Münster strategies.
authors.affiliation: Department of Pediatrics, University Children's Hospital, Kiel, Germany. martin.stanulla@uk-sh.de
authors.forename: Martin
authors.initials: M
authors.lastname: Stanulla
authors.forename: Elke
authors.initials: E
authors.lastname: Schaeffeler
authors.forename: Anja
authors.initials: A
authors.lastname: Möricke
authors.forename: Sally A
authors.initials: SA
authors.lastname: Coulthard
authors.forename: Gunnar
authors.initials: G
authors.lastname: Cario
authors.forename: André
authors.initials: A
authors.lastname: Schrauder
authors.forename: Peter
authors.initials: P
authors.lastname: Kaatsch
authors.forename: Michael
authors.initials: M
authors.lastname: Dördelmann
authors.forename: Karl
authors.initials: K
authors.lastname: Welte
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.forename: Alfred
authors.initials: A
authors.lastname: Reiter
authors.forename: Michel
authors.initials: M
authors.lastname: Eichelbaum
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Riehm
authors.forename: Martin
authors.initials: M
authors.lastname: Schrappe
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwab
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D001215:Asparaginase / Q000008:administration & dosage / Q000009:adverse effects; D001932:Brain Neoplasms / Q000201:enzymology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003630:Daunorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D005858:Germany; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology* / Q000235:genetics; D008297:Male; D008780:Methyltransferases / Q000235:genetics* / Q000378:metabolism; D016609:Neoplasms, Second Primary / Q000201:enzymology / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D012307:Risk Factors; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D014750:Vincristine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D001215:Asparaginase; D011241:Prednisone; D003630:Daunorubicin