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Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Effects of nilotinib on leukaemia cells using vibrational microspectroscopy and cell cloning
M R Siddique1, A V Rutter, K Wehbe
1Institute for Science and Technology in Medicine, Keele University, Guy Hilton Research Centre, Thornburrow Drive, Stoke on Trent ST4 7QB, UK. josep.sulesuso@uhns.nhs.uk.
Abstract:
Over the last few years, both synchrotron-based FTIR (S-FTIR) and Raman microspectroscopies have helped to better understand the effects of drugs on cancer cells. However, cancer is a mixture of cells with different sensitivity/resistance to drugs. Furthermore, the effects of drugs on cells produce both chemical and morphological changes, the latter could affect the spectra of cells incubated with drugs. Here, we successfully cloned sensitive and resistant leukaemia cells to nilotinib, a drug used in the management of leukaemia. This allowed both the study of a more uniform population and the study of sensitive and resistant cells prior to the addition of the drug with both S-FTIR and Raman microspectroscopies. The incubation with nilotinib produced changes in the S-FTIR and Raman spectra of both sensitive and resistant clones to nilotinib. Principal component analysis was able to distinguish between cells incubated in the absence or presence of the drug, even in the case of resistant clones. The latter would confirm that the spectral differences between the so-called resistant clonal cells prior to and after adding a drug might reside on those more or less sensitive cells that have been able to remain alive when they were collected to be studied with S-FTIR or Raman microspectroscopies. The data presented here indicate that the methodology of cell cloning can be applied to different types of malignant cells. This should facilitate the identification of spectral biomarkers of sensitivity/resistance to drugs. The next step would be a better assessment of sensitivity/resistance of leukaemia cells from patients which could guide clinicians to better tailor treatments to each individual patient.
Insights
Cloning leukemia cells identified spectral biomarkers for drug sensitivity. Synchrotron-based FTIR (S-FTIR) and Raman microspectroscopy distinguished drug-treated cells, aiding personalized cancer treatment strategies.
Area of Science:
- Biomedical Spectroscopy
- Cancer Cell Biology
- Pharmacogenomics
Background:
- Cancer heterogeneity poses challenges for drug efficacy.
- Synchrotron-based FTIR (S-FTIR) and Raman microspectroscopy analyze drug effects on cancer cells.
- Cellular response to drugs involves chemical and morphological changes impacting spectral data.
Purpose of the Study:
- To clone sensitive and resistant leukemia cell lines to nilotinib for uniform population studies.
- To investigate spectral changes in sensitive and resistant cells upon nilotinib treatment using S-FTIR and Raman microspectroscopy.
- To identify spectral biomarkers for drug sensitivity and resistance in leukemia.
Main Methods:
- Cell cloning of sensitive and resistant leukemia cell lines.
- Incubation of cloned cells with nilotinib.
- Analysis of spectral data using Synchrotron-based FTIR (S-FTIR) and Raman microspectroscopy.
- Principal Component Analysis (PCA) for spectral data interpretation.
Main Results:
- Nilotinib treatment induced spectral changes in both sensitive and resistant leukemia clones.
- PCA successfully differentiated between drug-treated and untreated cells, including resistant clones.
- Spectral differences in resistant cells post-treatment suggest the presence of subpopulations with varying drug sensitivity.
Conclusions:
- Cell cloning coupled with S-FTIR and Raman microspectroscopy can identify spectral biomarkers for drug sensitivity/resistance.
- This methodology holds promise for application to various cancer types.
- Future work can guide personalized leukemia treatment by assessing patient-specific drug sensitivity.

