Multidrug resistance protein 4 (MRP4) polymorphisms impact the 6-mercaptopurine dose tolerance during maintenance therapy in Japanese childhood acute lymphoblastic leukemia.
Pharmacogenomics J
; 15(4): 380-4, 2015 Aug.
Article
in En
| MEDLINE
| ID: mdl-25403995
ABSTRACT
Multidrug resistance protein 4 (MRP4) is involved in the efflux of nucleoside derivatives and has a role in the determination of drug sensitivity. We investigated the relationship between MRP4 genetic polymorphisms and doses of the 6-mercaptopurine (6-MP) and methotrexate. Further, we evaluated the frequency of therapeutic interruption during maintenance therapy in Japanese children with acute lymphoblastic leukemia (ALL). Ninety-four patients received an initial 6-MP dose in the range of 30-50 mg m(-2) in this analysis. Patients with homozygous variant allele in any of MRP4 G2269A, C912A and G559T required high frequency of 6-MP dose reduction compared with non-homozygous individuals. Average 6-MP dose for patients with homozygous variant allele on either MRP4 or inosine triphosphate pyrophosphatase was significantly lower than that for patients with non-homozygous variant allele during maintenance therapy (30.5 versus 40.0 mg m(-2), P=0.024). Therefore, MRP4 genotyping may be useful for personalizing the therapeutic dose of 6-MP during the ALL maintenance therapy in Japanese.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polymorphism, Genetic
/
Multidrug Resistance-Associated Proteins
/
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/
Mercaptopurine
/
Antimetabolites, Antineoplastic
Limits:
Child, preschool
/
Female
/
Humans
/
Male
Country/Region as subject:
Asia
Language:
En
Journal:
Pharmacogenomics J
Journal subject:
BIOLOGIA MOLECULAR
/
FARMACOLOGIA
Year:
2015
Document type:
Article
Affiliation country:
Japón