title: Characterization of Drug Effect on Leukemia Cells Through Single Cell Assay With Optical Tweezers and Dielectrophoresis.
abstract: 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.
authors: Jundi
authors: J
authors: Hou
authors: Tao
authors: T
authors: Luo
authors: Ka Lam
authors: KL
authors: Ng
authors: Anskar Y H
authors: AY
authors: Leung
authors: Raymond
authors: R
authors: Liang
authors: Dong
authors: D
authors: Sun
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001596:Benzylamines; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D018920:Coculture Techniques; D000080027:Cyclams; D004586:Electrophoresis / Q000379:methods*; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D052898:Optical Tweezers; D019718:Receptors, CXCR4 / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D059010:Single-Cell Analysis / Q000379:methods*; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D001596:Benzylamines; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; C088327:plerixafor