Thesis (Ph.D.) - Cairo University - Faculty of Science - Department of Biochemistry

Background: Acute Myeloid Leukemia (AML) is a heterogeneous disorder with variable genetic abnormalities and cytogenetic alterations which provide a significant disease prognosis and determine response to therapy. Purpose: We aim to investigate the expression of the MDR1 gene in 100 Egyptian AML patients, to identify their role on both the progression and chemotherapeutic refractoriness together with assessment of known prognostic molecular markers; FLT3-ITD and NPM1 mutations. Methodology: Quantitative assessment of MDR1 gene expression was performed by quantitative RTPCR. Additional prognostic molecular markers were determined as internal tandem duplications of the FLT 3 gene and nucleophosmin gene mutation A.Results: MDR1 gene expression levels & FLT3/ITD mutations were significantly higher in AML patients with resistant disease with P value <0.001 & 0.002 respectively. However, NPM1 was insignificantly higher in patients with CR P-value 0.14. In MDR positive group, wild FLT3/ITD with or without NPM1 mutation was favorable in achieving CR with p value 0.02. MDR negative group, wild FLT3/ITD with or without NPM1 mutation showed insignificantly higher CR rates with P value (0.35). Kaplan-Meier curves revealed statistically significant difference between MDR1- negative and MDR1-positive patients regarding their DFS and OS between the two groups where DFS & OS were higher in MDR1-negative patients with p value 0.004 & 0.01, respectively. Conclusion: the results obtained by the current work together with the previous researches concerning the study of multidrug resistance genes in AML patients provide additional evidence of the role played by these genes as predictors of chemoresistance and poor treatment outcome

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