Raman microscopy and Fourier transform infrared imaging can distinguish between apoptotic and nonapoptotic responses to the leukemia drug venetoclax in cell-line models, according to a new study.
The researchers combined the two vibrational spectroscopy techniques with chemometric analysis to examine biochemical changes in Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia cells. Their study focused on two cell lines with different intrinsic responses to venetoclax: BV-173, which is sensitive to the drug, and SD-1, which is resistant.
Venetoclax inhibits BCL-2, a protein that helps cancer cells evade apoptosis. Although the drug is used to treat some blood cancers, resistance remains a challenge, and the biochemical processes involved are not always fully understood.
The team treated both cell lines with 10 or 100 nM venetoclax for four or 24 hours. Raman microscopy and FT-IR imaging were then used to examine treatment-associated changes in nucleic acids, proteins, and lipids. Apoptosis was independently assessed using cell viability measurements, cleaved PARP-1 detection, and protein profiling.
In the sensitive BV-173 cells, spectroscopic changes appeared after four hours and became more pronounced after 24 hours. Early changes included stronger nucleic-acid-associated signals, reduced protein content, and lipid reorganization. After 24 hours, the spectra indicated protein degradation and aggregation, increased phospholipid content, and DNA loss – features consistent with later-stage apoptosis.
The resistant SD-1 cells produced a different spectroscopic profile. Their spectra indicated changes in protein conformation and lipid composition, while the structural integrity of proteins, lipids, and nucleic acids was largely maintained. The researchers interpreted this pattern as a treatment-associated response distinct from the apoptosis observed in BV-173 cells.
The findings suggest that combining Raman and FT-IR measurements could provide a label-free means of examining biochemical phenotypes associated with drug response. However, the work was limited to two cell lines, and substantial variability between biological replicates required additional spectral preprocessing.
The authors also caution that individual spectral bands cannot be assigned exclusively to particular molecules or biological pathways. Studies involving additional leukemia models and patient-derived samples, supported by techniques such as proteomics and lipidomics, will be needed to test the wider relevance of the observed signatures.
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