Investigating Collateral Sensitivity of AML

Abstract

Acute Myeloid Leukemia (AML) has a historically low 5-year survival rate compared to other types of cancers. There are many subtypes of AML and despite it being a heterogeneous disease, is often treated with a one-size-fits-all approach. Furthermore, relapse after initial successful treatment is common. This project is investigating the collateral sensitivity of AML by developing chemotherapy resistant cultured AML cells and then treating them with secondary chemotherapies to determine if the combination has a synergistic effect. Cabazitaxel is a chemotherapy drug used clinically to treat AML. Experiments using MOLM-13 cells in GI50 assays with Cabazitaxel were conducted to determine initial sensitivity. Currently, cells are being micro-dosed with increasing concentrations of Cabazitaxel, starting with their GI10 value. Cells are continuously cultured in in either Cabazitaxel or DMSO, as a control. GI50 assays will be re-run when treated cells resume growth rates of untreated cells in order to determine the extent of resistance. Once cell lines that are stable and non-reactive to the addition of the initial chemotherapy, a matrix of secondary chemotherapies will be applied to the resistant cell lines. Secondary treatments that successfully trigger apoptosis in the majority of resistant cells would show promise in collateral sensitivity and fighting chemotherapy resistance. By determining the collateral sensitivity of AML lines it will allow future research to be done on the effectiveness of secondary treatments for patients that have AML recurrence that is found to be resistant to in initial treatment.