Ps934 Novel Pharmacogenomic and Pharmacotranscriptomic Markers in Pediatric Acute Lymphoblastic Leukemia

Abstract

Background: Human T-cell Leukemia virus type I (HTLV-1) is a retrovirus that infects peripheral T cells and causes several refractory diseases like HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/ TSP) and adult T-cell leukemia (ATL). Recently, Drug repositioning, the application of available drugs for treating conditions different from the original treatment purposes, has become a popular drug development strategy mainly because of the reduced development time and cost. A recent study demonstrated the strong cytotoxic effect of Abacavir, a nucleoside analog reverse transcriptase inhibitor for HIV-1, on ATL cells. Previous studies also reported that HIV integrase inhibitors (INIs) prevented HTLV-1 integration, but the effect of HIV IN inhibitors on HTLV-1-infected cell survival remains unclear. Aims: To investigate the cytotoxic effect of MK-2048, a second-generation HIV-1 INI, on HTLV-1 infected cells. Methods: HTLV-1 infected cell lines and ATL derived cell lines were treated with six different HIV INIs (BMS-707035, Raltegravir, Elvitegravir, Cabotegravir, Dolutegravir, and MK-2048) and the number of viable cells 0-4 days after the treatment was measured by a luminescence assay (Cell Titer). Subsequently, the effect of MK-2048 on HTLV-1 infected cells was evaluated by cell cycle (FACS) and apoptosis (Caspase-3/7 activity).