An Innovative Epigenetic Merge in Treatment of AML Patients Correlates with Better "Molecular and Clinical” Outcomes | ||
| Egyptian Academic Journal of Biological Sciences. C, Physiology and Molecular Biology | ||
| Article 13, Volume 2, Issue 2, December 2010, Pages 115-129 PDF (529.1 K) | ||
| Document Type: Original Article | ||
| DOI: 10.21608/eajbsc.2010.16270 | ||
| Authors | ||
| Rola M. Ghorab; Mohammad F. Kamel | ||
| Clin. Biochemistry Dep., Alexandria Faculty of Science, Bagdad st., Moharam Bec, P.O. 21547, Alex., Egypt | ||
| Abstract | ||
| Purpose: Epigenetic gene silencing due to promoter hypermethylation& histone acetylation influence various molecular pathways in leukemogenesity of Acute Myeloid Leukemia (AML). Combined use of DNA methyltransferases & histone deacetylases inhibitors proved to reverse the methylomic phenotype of myeloid blasts & improve patient's prognosis. The study recruited 68 Adults patients 45 received novel combination of the HDACi valproic acid +/- the Dnmt1 inhibitor; epigallocatechingallate “EGCG” parallel to standard chemotherapy for 2 successive cycles. Results: We recorded; 37/45 (CR), 7 (PR) &1 (RF), 60% MRD elimination. Decreased Dnmt1 & HDAC1 activities (p<0.001). Reversed P15INK4B gene methylation & expression states 58 %, (p<0.02) & decreased levels of VEGF, bfgf, IL-6, NF-KB, TNF, COX-2 & P65 cytokines levels in a harmonized orchestra (p<0.01). Survival analyses showed high significant 2 years DFS (P<0.01). Conclusion: The used epi-drug combination distinctively exerted a destructive impact on AML blasts interpreted to tumor regression, better hematological & clinical response. | ||
| Keywords | ||
| DFS: disease free survival; Dnmt1 DNA methyltransferases1; HDACi: histone deacetylases inhibitor; MRD: inimal residual disease; VEGF: vascular endothelial growth factor; NF-KB: nuclear factor KB | ||
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