Integrin Antibody Decreases Deformability of Patient-Derived Pre-B Acute Lymphocytic Leukemia Cells as Measured by High-Frequency Acoustic Tweezers

J Ultrasound Med. 2020 Mar;39(3):589-595. doi: 10.1002/jum.15139. Epub 2019 Oct 21.

Abstract

Objectives: This article reports a study of cell mechanics in patient-derived (primary) B-cell acute lymphocytic leukemia (ALL) cells treated with antibodies against integrins. Leukemia cell adhesion to stromal cells mediates chemotherapeutic drug resistance, also known as cell adhesion-mediated chemotherapeutic drug resistance. We have previously shown that antibodies against integrin α4 and α6 adhesion molecules can de-adhere ALL cells from stromal cells or counter-receptors. Because drug-resistant cells are more deformable, as evaluated by single-beam acoustic tweezers, we hypothesized that changes in cell mechanics might contribute to the de-adhesive effect of integrin-targeting antibodies.

Methods: In this study, the deformability of primary pre-B ALL cells was evaluated by single-beam acoustic tweezers after treatments with the de-adhering antibody Tysabri or P5G10 against integrin α4 and α6 adhesion molecules.

Results: We demonstrated that primary ALL cells treated with P5G10 expressed decreased deformability compared with immunoglobulin G1 -treated control cells (P < .05). Tysabri did not show an effect on deformability (P > .05).

Conclusions: These results suggest that decreased deformability is associated with an integrin α6 blockade. Further assessments of the functional roles of deformability and integrin blockades in B-ALL cell drug resistance and deformability, respectively, are necessary.

Keywords: acoustic tweezers; acute lymphoblastic leukemia; antibody; deformability; drug resistance; integrins.

MeSH terms

  • Acoustics
  • Cell Adhesion / drug effects*
  • Cells, Cultured
  • Humans
  • Immunoglobulin G / administration & dosage
  • Immunologic Factors / therapeutic use*
  • Integrins / drug effects*
  • Natalizumab / therapeutic use*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / diagnostic imaging*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Ultrasonography / methods

Substances

  • Immunoglobulin G
  • Immunologic Factors
  • Integrins
  • Natalizumab