Individualized Multidrug Resistance In Acute Myeloid Leukemia

Abstract 2491 While much has been discovered in the laboratory regarding the mechanisms of multidrug resistance (MDR), based on phase III clinical trials of ATP-binding cassette (ABC) transporter modulators, these findings have not resulted in appreciable clinical benefit in acute myeloid leukemia (AML) patients. In this pilot study, we investigated the clinical relevance of 380 genes related to MDR in 31 samples from AML patients who had undergone conventional treatment, with 11 patients contributing samples at diagnosis and relapse, using TaqMan Low Density Arrays (TLDA). We and others have shown that the TaqMan-based qRT-PCR is superior to microarrays and SYBR-green-based qRT-PCR because of higher sensitivity and specificity in determining expression of highly homologous gene family members, such as the ABC transporters. 380 genes involved in metabolism, signal transduction, DNA repair, stress response, tumor suppressor activity, oncogenic transformation, apoptosis, and drug uptake or efflux were curated based on their potential role in MDR in the current literature. We found expression of four genes previously unreported in AML in both diagnostic and relapsed patient samples to correlate with duration of complete remission (CR) of induction chemotherapy: SLC7A8 and HSPE1 correlate negatively while GBP1 and ABCD2 correlate positively with CR duration (>2-fold change relative to the median, p2-fold change relative to the median, p2 fold change compared to diagnosis, p2 fold change compared to diagnosis, p Disclosures: No relevant conflicts of interest to declare.