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Raman classification of selected subtypes of acute lymphoblastic leukemia (ALL)
Ist Teil von
Analyst (London), 2024-01, Vol.149 (2), p.571-581
Ort / Verlag
England: Royal Society of Chemistry
Erscheinungsjahr
2024
Quelle
MEDLINE
Beschreibungen/Notizen
B-cell precursor acute lymphoblastic leukemia (BCP-ALL) with chromosome translocations like
KMT2A
gene rearrangement (KMT2A-r) and
BCR-ABL1
fusion gene have been recognized as crucial drivers in both BCP-ALL leukemogenesis and treatment management. Standard diagnostic protocols for proliferative diseases of the hematopoietic system, like KMT2A-r-ALL, are genetically based and strongly molecularly oriented. Therefore, an efficient diagnostic procedure requires not only experienced and multidisciplinary laboratory staff but also considerable instrumentation and material costs. In recent years, a Raman spectroscopy method has been increasingly used to detect subtle chemical changes in individual cells resulting from stress or disease. Therefore, the objective of this study was to identify Raman signatures for the molecular subtypes and to develop a classification method based on the unique spectroscopic profile of
in vitro
models that represent specific aberrations aimed at
KMT2A-r
(RS4;11, and SEM) and the
BCR-ABL1
fusion gene (SUP-B15, BV-173, and SD-1). Data analysis was based on chemometric methods,
i.e.
principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and support vector machine (SVM). The PCA-based multivariate model was used for pattern recognition of each investigated group of cells while PLS-DA and SVM were used to build models for the discrimination of spectra from the studied BCP-ALL molecular subtypes. The results showed that the studied molecular subtypes of ALL have characteristic spectroscopic profiles reflecting their peculiar biochemical state. The content of lipids (1600 cm
−1
), nucleic acids (789 cm
−1
), and haemoproteins (754, 1130, and 1315 cm
−1
), which are crucial in cell metabolism, was indicated as the main source of differentiation between subtypes. Identification of spectroscopic markers of cells with
BCR-ABL1
or
KMT2A
-r may be useful in pharmacological studies to monitor the effectiveness of chemotherapy and further to understand differences in molecular responses between leukemia primary cells and cell lines.
Single cell and Raman-based classification of two high-risk acute lymphoblastic leukemia:
KMT2A
gene rearrangement (
KMT2A-r
) and
Philadelphia
chromosome (
Ph
+).