title: Chemotherapy exposure increases leukemia cell stiffness.
abstract: Deformability of blood cells is known to influence vascular flow and contribute to vascular complications. Medications for hematologic diseases have the potential to modulate these complications if they alter blood cell deformability. Here we report the effect of chemotherapy on leukemia cell mechanical properties. Acute lymphoblastic and acute myeloid leukemia cells were incubated with standard induction chemotherapy, and individual cell stiffness was tracked with atomic force microscopy. When exposed to dexamethasone or daunorubicin, leukemia cell stiffness increased by nearly 2 orders of magnitude, which decreased their passage through microfluidic channels. This stiffness increase occurred before caspase activation and peaked after completion of cell death, and the rate of stiffness increase depended on chemotherapy type. Stiffening with cell death occurred for all cell types investigated and may be due to dynamic changes in the actin cytoskeleton. These observations suggest that chemotherapy itself may increase the risk of vascular complications in acute leukemia.
authors.affiliation: Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of California-San Francisco, San Francisco, CA, USA.
authors.forename: Wilbur A
authors.initials: WA
authors.lastname: Lam
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rosenbluth
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Fletcher
mesh_terms: D000199:Actins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D003630:Daunorubicin / Q000009:adverse effects / Q000494:pharmacology*; D003907:Dexamethasone / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D019169:Jurkat Cells; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D046210:Microfluidic Analytical Techniques; D018625:Microscopy, Atomic Force; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D014652:Vascular Diseases / Q000139:chemically induced
chemical_list: D000199:Actins; D003907:Dexamethasone; D003630:Daunorubicin