Exploring Biochemical Characteristics of Pediatric Hyperdiploid Acute Lymphoblastic Leukemia by Raman Spectroscopy

Area of Science:

• Biomedical Optics
• Molecular Biology
• Hematology

Background:

• Hyperdiploid (HD) B-cell acute lymphoblastic leukemia (ALL) is the most common subtype, yet patient relapse indicates underlying biological heterogeneity.
• Existing genomic and epigenetic methods struggle to rapidly assess both metabolic state and chromosomal content in individual HD B-ALL cells.

Purpose of the Study:

• To introduce and validate a novel Raman spectroscopy (RS)-based approach for single-cell analysis of HD B-ALL.
• To demonstrate RS's capability in distinguishing HD B-ALL from normal B cells and other ALL subtypes.
• To develop a predictive model linking spectroscopic data to genomic aberrations.

Main Methods:

• Utilized Raman spectroscopy to detect biochemical signatures (nucleic acids, proteins, lipids) in single cells.
• Applied a partial least-squares regression (PLS-R) model to predict chromosome number from Raman spectra.
• Compared RS performance against established molecular subtypes: TCF3-PBX1, KMT2A-r, BCR-ABL1, and TEL-AML1.

Main Results:

• RS successfully differentiated malignant HD B-ALL cells from normal B cells.
• Spectroscopic signatures enabled discrimination between HD B-ALL and other major ALL molecular subtypes.
• The PLS-R model accurately predicted chromosome number from individual cell Raman spectra, correlating spectral fingerprints with genomic alterations.

Conclusions:

• Raman spectroscopy is a powerful, noninvasive tool for quantifying chromosomal alterations and metabolic phenotypes in HD B-ALL.
• This integrative approach captures disease heterogeneity, offering insights into complex biology.
• The findings pave the way for broader applications of RS in precision medicine for leukemia.