A Novel 5-Probe FISH Strategy is Better Equipped for a More Comprehensive and Cost-Effective Risk Stratification of...

Area of Science:

• Hematology
• Molecular Diagnostics
• Oncology

Background:

• Treatment protocols for B-cell precursor acute lymphoblastic leukemia (BCP-ALL) are increasingly tailored to genetic profiles and treatment response.
• Accurate risk stratification is crucial for optimizing BCP-ALL patient management.
• Existing diagnostic tools may have limitations in comprehensively identifying genetic abnormalities.

Purpose of the Study:

• To introduce and evaluate a novel five-probe Fluorescence In Situ Hybridization (FISH) strategy for BCP-ALL risk stratification.
• To compare the efficacy of the five-probe FISH strategy against the triple trisomy probe strategy in detecting high hyperdiploidy.
• To assess the capability of the new strategy in identifying clinically relevant genetic rearrangements in BCP-ALL.

Main Methods:

• Screening of 380 newly diagnosed BCP-ALL cases using a five-probe FISH panel.
• The panel included probes for BCR::ABL1, ETV6::RUNX1 fusions, and KMT2A, IgH, and CRLF2 rearrangements.
• Comparison with a triple trisomy probe (4p11/CEN10/17) for aneuploidy detection in a subset of cases.

Main Results:

• The five-probe FISH strategy assigned risk groups to approximately two-thirds of the 380 BCP-ALL patients.
• Concordant findings were observed in 75.5% of cases when compared to the triple trisomy probe strategy.
• The triple trisomy probe failed to detect high hyperdiploidy in 24.5% of patients; IgH rearrangement (non-CRLF2) was found in 5.3%.

Conclusions:

• The proposed five-probe FISH strategy provides more comprehensive risk stratification for BCP-ALL.
• This novel strategy demonstrates superior ability in identifying high hyperdiploidy.
• The five-probe FISH approach also aids in detecting a subset of Ph-like BCP-ALL cases.