Rapid Testing of Drug Resistant BCR-ABL(+) Leukemia Cells

Biosense Technologies, Inc., Woburn MA

Investigators

Abstract

DESCRIPTION (provided by applicant): Resistance to chemotherapeutic drugs is an ongoing problem that results in eventual treatment failures or suboptimal patient outcomes. Approximately one-quarter of BCR-ABL(+) leukemia patients demonstrate evidence of resistance to imatinib mesylate either at initial diagnosis or at some point after treatment has begun. In our Phase I investigation, we demonstrated that monitoring the cellular stress developed by BCR-ABL(+) leukemia cells in response to tyrosine kinase inhibiting (TKI) drugs can used as an early marker for determining the effect of the therapeutic agents on the cancer cells. The approach is optimally implemented by measuring the dielectric permittivity of drug-treated cell suspensions using differential impedance sensing. Corresponding measurements of drug-sensitive and drug-resistant BCR-ABL(+) cell lines were obtained and confirmed by MTT assay. The response of non-leukemic peripheral blood mononuclear cells (PBMCs) to TKIs measured at clinically relevant drug concentrations showed no significant background level. Finally, the responses of BCR-ABL(+) patient blood to different TKIs were consistent with our initial cell line measurements laying the foundation for a practical clinical assay. In this Phase I effort we propose to quantify the cellular stress related drug responses enabling ease in interpretation of results, develop prototype instrumentation, verify the technical approach through animal model measurements and demonstrate feasibility with patient samples.