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

Christophe Sandt1, Olivier Feraud2, Marie-Laure Bonnet2

  • 1SOLEIL Synchrotron, Saint Aubin, 91192, Gif sur Yvette, France.

Biochemical and Biophysical Research Communications
|July 31, 2018
PubMed

Insights

Fourier transform infrared (FTIR) microspectroscopy rapidly identifies the T315I mutation in chronic myeloid leukemia (CML) cells. This technique offers a new tool for early detection and drug screening of resistant CML.

Area of Science:

  • Biomedical Spectroscopy
  • Oncology
  • Molecular Biology

Background:

  • Tyrosine kinase inhibitors (TKI) are successful in treating chronic myeloid leukemia (CML).
  • Therapy resistance in CML can arise from mutations in the BCR-ABL oncogene's ABL-kinase domain.
  • The T315I mutation, a "gatekeeper" mutation, confers resistance to most TKIs, except Ponatinib.

Purpose of the Study:

  • To investigate Fourier transform infrared (FTIR) microspectroscopy as a method for identifying the T315I mutation in BCR-ABL.
  • To explore the potential of FTIR microspectroscopy for early detection and drug screening in CML.

Main Methods:

  • Utilized Fourier transform infrared (FTIR) microspectroscopy for single-cell analysis.
  • Employed Dox-inducible T315I-mutated BCR-ABL-expressing human UT-7 cells and murine embryonic stem cells for validation.
  • Performed transcriptome analysis to identify molecular signatures associated with the T315I mutation.

Main Results:

  • FTIR microspectroscopy successfully identified a unique spectral signature in single cells expressing the T315I-mutated BCR-ABL.
  • The specificity of the spectral signature was confirmed in engineered cell lines.
  • Transcriptome analysis revealed molecular differences linked to metabolic changes underlying the observed spectral signature.

Conclusions:

  • FTIR microspectroscopy is a powerful tool for rapid, single-cell identification of the T315I BCR-ABL mutation.
  • This methodology holds promise as a novel early detection tool for CML mutant clones.
  • The technique can potentially be applied to drug screening strategies targeting T315I-mutated CML cells.
Keywords:
BCR-ABLCMLInfrared microspectroscopyT315I

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