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 Blood, 15 April 2007, Vol. 109, No. 8, pp. 3505-3508.
Prepublished online as a Blood First Edition Paper on December 19, 2006; DOI 10.1182/blood-2006-08-043570.

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Submitted August 25, 2006
Accepted December 4, 2006

Chemotherapy exposure increases leukemia cell stiffness

Wilbur A. Lam, Michael J. Rosenbluth, and Daniel A. Fletcher*

Dept of Pediatrics, Division of Pediatric Hematology/Oncology, University of California, San Francisco, CA
Dept of Bioengineering, & UCSF/UCB Joint Graduate Group in Bioengineering, UC Berkeley, Berkeley, CA
Biophysics Graduate Group, UC Berkeley, Berkeley, CA

* Corresponding author; email: fletch{at}berkeley.edu.

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 two 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.


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