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

Journal Article · Sat Sep 15 04:00:00 EDT 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.07.127· OSTI ID:23105584

Sandt, Christophe ^[1]; Feraud, Olivier; Bonnet, Marie-Laure; Desterke, Christophe; Khedhir, Rania ^[2]; others, and

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1. SOLEIL Synchrotron, Saint Aubin, 91192, Gif sur Yvette (France)
2. INSERM UMR_S_935, Campus CNRS, Villejuif (France)

Highlights: • BCR-ABL T315I mutation can be detected in single leukemic cells using infrared microspectroscopy. • The specificity of this spectral signature is demonstrated using Dox-inducible T315I-mutated BCR-ABL expressing cell lines. • Leukemic cells expressing T315I-mutated BCR-ABL exhibit a distinct transcriptome signature. • This technology could be applied to rapid detection of leukemic cells expressing T315I and to drug screening strategies. 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.

• OSTI ID: 23105584
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 503; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
MYELOID LEUKEMIA
ONCOGENES
STEM CELLS
TYROSINE