Chemotherapeutic Resistance in Egyptian Acute Myeloid Leukemia Patients

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