Characterization of Drug Effect on Leukemia Cells Through Single Cell Assay With Optical Tweezers and Dielectrophoresis

One of the greatest challenges in acute myeloid leukemia (AML) treatment is preventing relapse. Leukemia cells can hide in bone marrow niche or vascular niche. Hence, many chemical drugs cannot kill these cells. To characterize migration and adhesion properties of leukemia cells in specific niches, CXCR4/SDF-1α signal pathway has been widely used for investigation. AMD3100 is treated as one of the most common chemical drugs that can inhibit this signal. In the current study, we particularly investigate the effect of AMD3100 on the adhesion property of leukemia cells on stromal cells by using engineering tools, namely, optical tweezers (OT) and dielectrophoresis (DEP), to probe single cell property. AMD3100 not only inhibits the CXCR4/SDF-1α signal pathway but also reduces gene expression of CXCR4 and VLA-4 on leukemia cells. The drug also softens leukemia cells. This work provides a new way to investigate cell behavior under drug treatment. The use of combined engineering tools will benefit drug discovery and assessment for leukemia treatment.

I. Introduction

Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells that is characterized by accumulation of immature malignant cells in the bone marrow. The high relapsed rate of AML disease indicates persistence of leukemia stem cells, which hide in specific niches in the body. The constituent of niches, such as cells, extracellular matrix (ECM), and soluble factors, can interact with leukemia stem cells to maintain their self-renewal ability and to protect them from environmental stress. The components of niches are complicated, and their roles in regulating hematopoietic stem cells and leukemia stem cells are important. Although the details on the protection mechanism of niches are still unclear, the importance of investigating interactions between niches and leukemia cells are well recognized.