Assessment of Multidrug Resistance Gene (MDR1) Expression in Iraqi Acute Myeloid Leukemic patients

MDR1gene expression upregulation has been shown to be associated with resistance to chemotherapy treatment in acute leukaemia. The aim of this study is to investigate the levels of MDR1 transcript by RTqPCR at different phases of AML, and correlate these levels with patients' response to chemotherapy treatment. We investigated mRNA levels of MDR1 in 31 newly diagnosis patients at presentation, 1st induction, 2nd induction and consolidation. The mean fold of 10 healthy voluntary blood controls was defined as cutoff value (1.1±0.03), with samples showing higher levels considered positive while those showing lower levels considered negative for MDR1 expression. At presentation, 6/31 (19.4%) and 25/31 (80.6%) were positive and negative for MDR1 expression respectively. After first induction 9/15 (60%) were MDR1 positive. 4/8 (50%) of patients tested positive for MDR1 upregulation after 2nd induction. After consolidation 1/3 (33.3%) showed upregulation of MDR1 transcription. Statistical analysis showed significant effect of mean fold for MDR1 expression in non-responder (NR) AML patients at presentation (2.74 fold ±0.12, P<0.01) compared to (0.34 fold ±0.02; 1.1 fold ±0.03) for complete remission (CR) and control respectively. However, there were no significant differences between CR and NR (p=0.768) after 1st induction. Early relapse cases showed highly significant effect for MDR1 expression in consolidation as compared to CR patients (1.66±0.05, p=0.033). There was progressively increased MDR1 expression in individual patients after 1st induction. Uneven distribution of MDR1 expression among FAB AML subtypes was detected, with highest level MDR1 expression detected in M2. In Conclusion our findings suggest that detection of positive MDR1 expression in newly diagnosis AML patients was associated with poor clinical outcome and with M2 subtype. MDR1 positivity in AML patients with CR at consolidation was associated with early relapse.