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Modeling Chemotherapy Resistant Leukemia In Vitro

Modeling Chemotherapy Resistant Leukemia In Vitro

Published on: February 9, 2016

Chemotherapy exposure increases leukemia cell stiffness.

Wilbur A Lam¹, Michael J Rosenbluth, Daniel A Fletcher

¹Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of California-San Francisco, San Francisco, CA, USA.

|December 21, 2006

Summary

Chemotherapy significantly increases leukemia cell stiffness, impairing their movement. This finding suggests that leukemia treatments may paradoxically heighten the risk of vascular complications.

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Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia

Published on: September 18, 2013

Area of Science:

Hematology
Biophysics
Cell Biology

Background:

Blood cell deformability impacts vascular flow and complications.
Chemotherapies for hematologic diseases may alter cell deformability, influencing disease outcomes.

Purpose of the Study:

To investigate the effect of chemotherapy on the mechanical properties of leukemia cells.
To determine if chemotherapy alters leukemia cell stiffness and passage through microchannels.

Main Methods:

Acute lymphoblastic leukemia and acute myeloid leukemia cells were treated with standard induction chemotherapy.
Individual cell stiffness was measured using atomic force microscopy.
Cellular passage through microfluidic channels was assessed.

Main Results:

Dexamethasone and daunorubicin treatment increased leukemia cell stiffness by nearly two orders of magnitude.
Increased cell stiffness reduced the ability of leukemia cells to pass through microfluidic channels.
Stiffening occurred before caspase activation, peaked after cell death, and varied by chemotherapy type, potentially linked to actin cytoskeleton changes.

Conclusions:

Chemotherapy significantly alters leukemia cell mechanical properties, increasing their stiffness.
This chemotherapy-induced stiffening may impede cellular passage, potentially increasing the risk of vascular complications in acute leukemia patients.