BCL2 gene polymorphism could predict the treatment outcomes in acute myeloid leukemia patients

Moon, Joon Ho; Sohn, Sang Kyun; Lee, Myung-Hoon; Jang, Jun Ho; Kım, Kihyun; Jung, Chul Won; Kim, Dong Hwan

doi:10.1016/j.leukres.2009.05.009

Cited by 30 publications

(27 citation statements)

References 23 publications

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“…Furthermore, their inhibition may sensitize cancer cells to other apoptotic stimuli resulting from DNA damage. 7 Previous studies have shown that these elevated expression of these proteins can inhibit cytotoxic responses to chemotherapeutic agents like Ara-C. [36][37][38] In this regard, our data suggests that exposure to Ara-C increases the transcription of antiapoptotic genes and this may be important in the development of drug resistance to this agent. [38][39][40] In contrast, the combination of SNS-032 and Ara-C significantly suppressed the transcription of these same antiapoptotic genes.…”

Section: Discussionmentioning

confidence: 60%

The cyclin-dependent kinase inhibitor SNS-032 has single agent activity in AML cells and is highly synergistic with cytarabine

et al. 2011

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) is a selective cyclin-dependent kinase (CDK) inhibitor. In this study, we evaluated its effects on primary acute myeloid leukemia (AML) samples (n ¼ 87). In vitro exposure to SNS-032 for 48 h resulted in a mean LD 50 of 139±203 nM; Cytarabine (Ara-C) was more than 35 times less potent in the same cohort. SNS-032-induced a dose-dependent increase in annexin V staining and caspase-3 activation. At the molecular level, SNS-032 induced a marked dephosphorylation of serine 2 and 5 of RNA polymerase (RNA Pol) II and inhibited the expression of CDK2 and CDK9 and dephosphorylated CDK7. Furthermore, the combination of SNS-032 and Ara-C showed remarkable synergy that was associated with reduced mRNA levels of the antiapoptotic genes XIAP, BCL2 and MCL1.In conclusion, SNS-032 is effective as a single agent and in combination with Ara-C in primary AML blasts. Treatment with Ara-C alone significantly induced the transcription of the antiapoptotic genes BCL2 and XIAP. In contrast, the combination of SNS-032 and Ara-C suppressed the transcription of BCL2, XIAP and MCL1. Therefore, the combination of SNS-032 and Ara-C may increase the sensitivity of AML cells to the cytotoxic effects of Ara-C by inhibiting the transcription of antiapoptotic genes.

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Section: Discussionmentioning

confidence: 60%

The cyclin-dependent kinase inhibitor SNS-032 has single agent activity in AML cells and is highly synergistic with cytarabine

et al. 2011

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“…Moon et al concluded that the Bcl 2 -938 C > A polymorphism was linked to overall survival and remission rates following chemotherapy in patients with leukemia. 16 Nückel et al in a study involving patients with chronic lymphocytic leukemia (CLL) found that in the Bcl 2 938 C > A polymorphism, the AA genotype was associated with an increased expression of Bcl 2 and that it may be appropriate to use this as a genetic prognostic marker in patients with CLL. 17 Hwan et al reported that there was a significant association between the Bcl 2-938 Table 1.…”

Section: Discussionmentioning

confidence: 99%

The role of certain gene polymorphisms involved in the apoptotic pathways in polycythemia vera and essential thrombocytosis

Dogru¹,

Ay²,

Ay³

et al. 2017

Adv Clin Exp Med

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“…Besides the fusion genes derived from chromosomal translocations, numerous gene mutations have also been reported in different types of AML. The genetic polymorphisms of several candidate genes have been reported to correlate to the susceptibility to AML in different ethnic populations [7,8]. Characterizing molecular mutations in AML is important for the management of patients individually.…”

Section: Introductionmentioning

confidence: 99%

The OPN Gene Polymorphism Confers the Susceptibility and Response to Ara-C Based Chemotherapy in Chinese AML Patients

Zhang¹,

Yang²,

Li³

et al. 2015

Cell Physiol Biochem

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Aim: To investigate the possible association between the Osteopontin (OPN) gene polymorphisms and the susceptibility and chemotherapy response of acute myeloid leukemia patients. Methods: A total of 381 patients with de nova AML and 430 healthy controls were enrolled. All patients received Ara-C-based standard induction chemotherapy regimens, and the treatment response was evaluated. Several polymorphisms in the human OPN encoding gene have been identified. The OPN) gene polymorphisms at 3 loci, namely, -156 GG>G, -443 C>T and -66T>G were determined. Results: We identified that the -443C>T polymorphism was the only one which is closely related to AML. Compared with the -443TT carriers, our data showed that the -443CC genotype carriers were significantly related to a higher risk for AML. The -443CC genotype was also more prevalent in poor response groups than in good response group. The -443CC carriers are more likely to have poor response to AML treatment. Cellular assay indicated that the leukemic cell lines receiving the OPN -443C transfection have a significantly lower apoptosis rate to Ara-C treatment compared to cell lines transfected with -443T. Conclusion: The findings of this study suggest OPN-443C>T gene polymorphism may be sued as a molecular for susceptibility and chemotherapy response of AML.

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BCL2 gene polymorphism could predict the treatment outcomes in acute myeloid leukemia patients

Cited by 30 publications

References 23 publications

The cyclin-dependent kinase inhibitor SNS-032 has single agent activity in AML cells and is highly synergistic with cytarabine

The cyclin-dependent kinase inhibitor SNS-032 has single agent activity in AML cells and is highly synergistic with cytarabine

The role of certain gene polymorphisms involved in the apoptotic pathways in polycythemia vera and essential thrombocytosis

The OPN Gene Polymorphism Confers the Susceptibility and Response to Ara-C Based Chemotherapy in Chinese AML Patients

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