Abstract

Single Cell Analysis on Acute Myleloid Leukemia Patient Cell Samples: Microfluidic Data Collection and Clinical Implications

Paul C H Li, Professor, Simon Fraser University

Acute myeloid leukemia (AML), which is a cancer of the myeloid line of blood cells, is usually treated by chemotherapy. However multidrug resistance (MDR) is the major cause of failure in cancer chemotherapy. MDR occurs when cancer cells resist against chemotherapeutic drugs by pumping drugs out the cells. P-glycoprotein (Pgp) and MRP1, subfamilies of the ABC transporter, are proteins that are responsible for the pumping. MDR inhibitors such as cyclosporine A (CsA), verapamil (VER), PSC 833 and MK571 can bind to MDR protein and stop it from functioning. The reversal effects of MDR inhibitors are investigated to improve chemotherapy sensitivity using a microfluidic chip designed to combine dielectrophoresis (DEP) with same-single-cell analysis (SASCA). Generally, SASCA is used to measure drug accumulation of daunorubicin (DNR) and the inhibition of efflux in MDR cancer cells, and the measurement is performed on the same single cell. Now we apply the method to patient cells, which are primary cells that are cryopreserved from AML patients’ liquid biopsy samples. The initial signals of cells obtained from non-responsive patients were low, and fold-increase in signal enhancement was found with MDR inhibitors. For the AML cells from patients with remission, the initial signal was high, and no fold-increase was found with the inhibitors. We envision the drug accumulation measured on single cryopreserved AML cells can provide information for clinical monitoring of patient undergoing chemotherapy in the future.