Role of the MDM2 Promoter Polymorphism (-309T>G) in Acute Myeloid Leukemia Development

Cingeetham, Anuradha; Vuree, Sugunakar; Jiwatani, Sangeeta; Kagita, Sailaja; Dunna, Nageswara Rao; Meka, Phanni Bhushann; Gorre, Manjula; Annamaneni, Sandhya; Digumarti, Raghunadharao; Sinha, Sudha; Satti, Vishnupriya

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자료유형: 학술저널

저자정보: Cingeetham, Anuradha (Department of Genetics, Osmania University) Vuree, Sugunakar (Department of Genetics, Osmania University) Jiwatani, Sangeeta (Nizam's Institute of Medical Sciences) Kagita, Sailaja (Nizam's Institute of Medical Sciences) Dunna, Nageswara Rao (School of Chemical and Biotechnology, SASTRA University) Meka, Phanni Bhushann (Department of Genetics, Osmania University) Gorre, Manjula (Department of Genetics, Osmania University) Annamaneni, Sandhya (Department of Genetics, Osmania University) Digumarti, Raghunadharao (Nizam's Institute of Medical Sciences) Sinha, Sudha (MNJ Institute of Oncology Regional Cancer Center) Satti, Vishnupriya (Department of Genetics, Osmania University)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제16권 제7호

발행연도: 2015.1

수록면: 2,707 - 2,712 (6page)

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Background: The human homologue of the mouse double minute 2 (MDM2) gene is a negative regulator of Tp53. MDM2-309T>G a functional promoter polymorphism was found to be associated with overexpression thereby attenuation of Tp53 stress response and increased cancer susceptibility. We have planned to evaluate the possible role of MDM2-309T>G polymorphism with risk and response to chemotherapy in AML. Materials and Methods: A total of 223 de novo AML cases and 304 age and sex matched healthy controls were genotyped for the MDM2-309T>G polymorphism through the tetra-primer amplification refractory mutation system (ARMS)-PCR method. In order to assess the functional relationship of -309T>G SNP with MDM2 expression level, we quantified MDM2 mRNA in 30 primary AML blood samples through quantitative RT-PCR. Both the (-309T>G) genotypes and the MDM2 expression were correlated with disease free survival (DFS) rates among patients who have achieved complete remission (CR) after first induction chemotherapy. Results: MDM2-309T>G polymorphism was significantly associated with AML development (p<0.0001). The presence of either GG genotype or G allele at MDM2-309 confered 1.79 (95% CI: 1.12-2.86; p<0.001) and 1.46 fold (95%CI: 1.14-1.86; p= 0.003) increased AML risk. Survival analysis revealed that CR+ve cases with GG genotype had significantly increased DFS rates (16months, p=0.05) compared to CR+ve TT (11 months) and TG (9 months) genotype groups. Further, MDM2 expression was also found to be significantly elevated in GG genotype patients (p=0.0039) and among CR+ve cases (p=0.0036). Conclusions: The MDM2-309T>G polymorphism might be involved in AML development and also serve as a good prognostic indicator.

#AML #MDM2 #tetra primer #ARMS) PCR #RT-PCR #disease free survival #complete remission

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