Chemotherapeutic Resistance in Egyptian Acute Myeloid Leukemia Patients

Abstract

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