Chemotherapeutic Resistance in Egyptian Acute Myeloid Leukemia Patients

Document Type: Research Articles

Authors

1 Department of Clinical and Chemical Pathology, Kasr Al Ainy Centre of Clinical Oncology and Nuclear Medicine, School of Medicine, Cairo University, Cairo, Egypt.

2 Molecular Oncology Unit, Kasr Al Ainy Centre of Clinical Oncology and Nuclear Medicine, School of Medicine, Cairo University, Cairo, Egypt.

3 Faculaty of Science, Cairo University, Cairo, Egypt.

Abstract

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 RT-PCR. 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 and FLT3/ITD mutations
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
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 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 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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