UNIGE document Scientific Article
previous document  unige:31211  next document
add to browser collection
Title

Polymorphism in multidrug resistance-associated protein gene 3 is associated with outcomes in childhood acute lymphoblastic leukemia

Authors
Sauty, G
Labuda, M
Gagné, V
Rousseau, J
Moghrabi, A
Laverdière, C
Sinnett, D
show hidden authors show all authors [1 - 9]
Published in The Pharmacogenomics Journal. 2012, vol. 12, no. 5, p. 386-94
Abstract Multidrug resistance-related proteins (MRPs) 2, 3 and 5 are involved in the efflux of drugs used in acute lymphoblastic leukemia (ALL) treatment. Polymorphisms of these genes were investigated for an association with treatment responses in 273 childhood ALL patients. The MRP3 A-189 allele of the regulatory AT polymorphism was associated with reduced event-free survival (P=0.01). The results remained significant after adjustment for multiple comparisons and in the multivariate analysis. Among patients with an event, the A-189 carriers had significantly higher methotrexate plasma levels (P=0.03). MRP3 A-189 also conferred four times higher risk of a relapse in central nervous system (P=0.01). Patients with this allele tended to have lower frequency of thrombocytopenia grade 2 (P=0.06). Gene reporter assay showed that the haplotype tagged by the A-189 had higher promoter activity (P≤0.01). In conclusion, MRP3 A-189 T polymorphism was associated with treatment responses in ALL, likely due to the change in MRP3 efflux.
Keywords AllelesBiomarkers, PharmacologicalDisease-Free SurvivalGenetic Association StudiesGenotypeHaplotypesHumansMethotrexate/therapeutic useMultidrug Resistance-Associated Proteins/genetics/metabolismPolymorphism, Single Nucleotide/geneticsPrecursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/geneticsTreatment Outcome
Identifiers
PMID: 21606946
Full text
Article (Published version) (445 Kb) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Research groups Groupe Ozsahin Ayse Hulya (onco-hémato pédiatrie) (889)
Plateforme d'oncologie et d'hématologie pédiatrique (907)
Citation
(ISO format)
ANSARI DJABERI, Marc Georges et al. Polymorphism in multidrug resistance-associated protein gene 3 is associated with outcomes in childhood acute lymphoblastic leukemia. In: The Pharmacogenomics Journal, 2012, vol. 12, n° 5, p. 386-94. https://archive-ouverte.unige.ch/unige:31211

179 hits

0 download

Update

Deposited on : 2013-11-20

Export document
Format :
Citation style :