Direct and rapid identification of T315I-Mutated BCR-ABL expressing leukemic cells using infrared microspectroscopy

Direct and rapid identification of T315I-Mutated BCR-ABL expressing leukemic cells using infrared microspectroscopy.

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Item Type: Article
Status: Published
Official URL:
Journal or Publication Title: Biochemical and Biophysical Research Communications
Volume: 503
Number: 3
Page Range: pp. 1861-1867
Date: 2018
Divisions: Gene and Stem Cell Therapy
Depositing User: General Admin
Identification Number: 10.1016/j.bbrc.2018.07.127
ISSN: 0006291X
Date Deposited: 03 Jan 2021 23:10

Despite the major success obtained by the use of tyrosine kinase inhibitors (TKI) in chronic myeloid leukemia (CML), resistances to therapies occur due to mutations in the ABL-kinase domain of the BCR-ABL oncogene. Amongst these mutations, the "gatekeeper" T315I is a major concern as it renders leukemic cells resistant to all licenced TKI except Ponatinib. We report here that Fourier transform infrared (FTIR) microspectroscopy is a powerful methodology allowing rapid and direct identification of a spectral signature in single cells expressing T315I-mutated BCR-ABL. The specificity of this spectral signature is confirmed using a Dox-inducible T315I-mutated BCR-ABL-expressing human UT-7 cells as well as in murine embryonic stem cells. Transcriptome analysis of UT-7 cells expressing BCR-ABL as compared to BCR-ABL T315I clearly identified a molecular signature which could be at the origin of the generation of metabolic changes giving rise to the spectral signature. Thus, these results suggest that this new methodology can be applied to the identification of leukemic cells harbouring the T315I mutation at the single cell level and could represent a novel early detection tool of mutant clones. It could also be applied to drug screening strategies to target T315I-mutated leukemic cells.

Keywords: BCR-ABL; CML; Infrared microspectroscopy; T315I.

Copyright © 2018 Elsevier Inc. All rights reserved.

Sandt, Christophe
Feraud, Olivier
Bonnet, Marie-Laure
Desterke, Christophe
Khedhir, Rania
Flamant, Stephane
Bailey, Charles G.
Rasko, John E.J.
Dumas, Paul
Bennaceur-Griscelli, Annelise
Turhan, Ali G.
Last Modified: 03 Jan 2021 23:10

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