Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
ASSOCIATION OF CYP3A4 GENOTYPE WITH TREATMENT-RELATED LEUKEMIA
Autore:
FELIX CA; WALKER AH; LANGE BJ; WILLIAMS TM; WINICK NJ; CHEUNG NKV; LOVETT BD; NOWELL PC; BLAIR IA; REBBECK TR;
Indirizzi:
CHILDRENS HOSP,LEONARD & MADLYN ABRAMSON PEDIAT RES CTR,DIV ONCOL,ROOM 902B,324 S 34TH ST PHILADELPHIA PA 19104 UNIV PENN,DEPT PEDIAT PHILADELPHIA PA 19104 UNIV PENN,CTR CLIN EPIDEMIOL & BIOSTAT,DEPT BIOSTAT & EPIDEMIOL PHILADELPHIA PA 19104 UNIV PENN,CTR CANC PHILADELPHIA PA 19104 UNIV PENN,SCH MED,DEPT PATHOL & LAB MED PHILADELPHIA PA 19104 UNIV PENN,SCH MED,CTR CANC PHARMACOL PHILADELPHIA PA 19104 CHILDRENS MED CTR,CTR CANC & BLOOD DISORDERS DALLAS TX 75235 MEM SLOAN KETTERING CANC CTR,DEPT PEDIAT NEW YORK NY 10021
Titolo Testata:
Proceedings of the National Academy of Sciences of the United Statesof America
fascicolo: 22, volume: 95, anno: 1998,
pagine: 13176 - 13181
SICI:
0027-8424(1998)95:22<13176:AOCGWT>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; 2ND MALIGNANT NEOPLASMS; DNA-TOPOISOMERASE-II; ALL-1 GENE; NEUROFIBROMATOSIS TYPE-1; CANCER SUSCEPTIBILITY; CYTOCHROME-P450 3A4; ALKYLATING-AGENTS; CHILDHOOD-CANCER;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
67
Recensione:
Indirizzi per estratti:
Citazione:
C.A. Felix et al., "ASSOCIATION OF CYP3A4 GENOTYPE WITH TREATMENT-RELATED LEUKEMIA", Proceedings of the National Academy of Sciences of the United Statesof America, 95(22), 1998, pp. 13176-13181

Abstract

Epipodophyllotoxins are associated with leukemias characterized by translocations of the MLL gene at chromosome band 11q23 and other translocations. Cytochrome P450 (CYP) 3A metabolizes epipodophyllotoxins andother chemotherapeutic agents. CYP3A metabolism generates epipodophyllotoxin catechol and quinone metabolites, which could damage DNA Thereis a polymorphism in the 5' promoter region of the CYP3A4 gene (CYP3A4-V) that might alter the metabolism of anticancer drugs, We examined 99 de novo and 30 treatment-related leukemias with a conformation-sensitive gel electrophoresis assay for the presence of the CYP3A4-V. In all treatment-related cases, there was prior exposure to one or more anticancer drugs metabolized by CYP3A, Nineteen of 99 de novo (19%) and 1 of 30 treatment-related (3%) leukemias carried the CYP3A4-V (P = 0.026; Fisher's Exact Test, FET), Nine of 42 de novo leukemias with MLL gene translocations (21%), and 0 of 22 treatment-related leukemias withMLL gene translocations carried the CYP3A4-V(P = 0.016, FET), This relationship remained significant when 19 treatment-related leukemias with MLL gene translocations that followed epipodophyllotoxin exposure were compared with the same 42 de novo cases (P = 0.026, FET), These data suggest that individuals with CYP3A4-W genotype may be at increasedrisk for treatment-related leukemia and that epipodophyllotoxin metabolism by CYP3A4 may contribute to the secondary cancer risk The CYP3A4-W genotype may increase production of potentially DNA-damaging reactive intermediates, The variant may decrease production of the epipodophyllotoxin catechol metabolite, which is the precursor of the potentially DNA-damaging quinone.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 08:58:07