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Fang Wang Li-wu Fu*

Multi-drug transporter ABCG2 gene polymorphisms and their prognostic value in patients with de novo acute leukemia. Fang Wang Li-wu Fu*.

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Fang Wang Li-wu Fu*

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  1. Multi-drug transporter ABCG2 gene polymorphisms and their prognostic value in patients with de novo acute leukemia Fang WangLi-wu Fu*

  2. The ATP-binding cassette subfamily G member 2 (ABCG2) gene, also known as breast cancer resistance protein (BCRP), was first identified as a multidrug resistance protein. ABCG2is widely expressed in many normaltissues, including intestine,placenta, mammary gland, brain,and liver, and has been shown toplay an important role against xenobiotics and their metabolites. The apical localization of ABCG2 in the intestinal epithelium and the bile canalicular membrane indicates a possible role of ABCG2 in intestinal absorption and hepatobiliary excretion of its substrates.

  3. ABCG2 can influence itsdrug efflux function and substrate specificity: ABCG2 variants R482G and R482T lose methotrexate-transporting activity but conferincreasedmitoxantroneresistance. The C421A polymorphism was associated with decreased protein expression and transport activity and altered pharmacokinetic parameters of some BCRP substrates

  4. In the present study: we exploredthe positions and frequencies ofSNPs in ABCG2and examined their possible prognostic impact in acute leukemia patients we analyzed the expression of ABCG2 using quantitative RT-PCR toinvestigate its potential role in clinical outcome of acute leukemia patients. wedeterminedthe functional activity of ABCG2 in isolated patients blast cells with flow cytometric assay

  5. Summary of ABCG2 SNPs detected in the passage

  6. OS and DFS were significantly longer in patients with the 34GG genotype than those with the 34GA/34AA genotype patients without BMT OS and DFS were significantly longer in patients with the 34GG genotype than those with the 34GA/34AA genotype in BMT patients OS and DFS of patients with the ABCG2 34GG genotype were influenced by other ABCG2 gene polymorphisms

  7. Patient cells were exposed to the indicated concentrations of vincristine, daunorubicin, doxorubicin and mitoxantrone for 72 h. Effects of BCRP expression and G34A polymorphism on the accumulation of doxorubicin and Rho 123.

  8. P-gp expression of the three patients was comparable to those of negative control. BCRP expression was low in patient 2 and 5 compared to the negative control S1 cells, whereas patient 8 showed marked BCRP overexpression.

  9. Conclusions six polymorphisms are identified in ABCG2, including one novel synonymous polymorphism in exon 16 with a low allele frequency (0.5%). Our data also shows that ABCG2 G34A polymorphism could bea potential independent prognostic factor in acute leukemia patients.The patients carrying 34GA/AA genotype displayed worse overall survival and shorter disease free survival than that with 34GG genotype

  10. Thank you!

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