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

The modern treatment protocols in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) are based on the disease's genetic characteristics and response to treatment. We propose a novel five-probe FISH strategy to risk stratify the BCP-ALL and compare its ability with the triple trisomy probe strategy to detect high hyperdiploidy.

All newly diagnosed BCP-ALL cases were investigated using a five-probe FISH panel that included probes targeting BCR::ABL1 fusion, ETV6::RUNX1 fusion, and break-apart probes for KMT2A, IgH, and CRLF2 rearrangements. Further, a selected number of cases were screened by the triple trisomy probe of 4p11/CEN10/17 (Zytovision, Bremerhaven, Germany) to identify aneuploidy.

Of the 380 patients of BCP-ALL screened (≤ 18 years: 57.9%; > 18 years: 42.1%) using this five-probe strategy, we could assign clinically relevant eight risk groups to almost two-thirds of the patients (similar to the available literature). Compared with the widely accepted triple trisomy probe strategy, we found concordant findings in 75.5% of the patients; the triple trisomy probe could not identify high hyperdiploidy in 24.5% of patients. We observed the presence of (non-CRLF2) IgH rearrangement in 5.3% of patients.

We conclude that the proposed five-probe FISH strategy is better equipped to more comprehensively risk stratify BCP-ALL patients, with an increased ability to identify high hyperdiploidy and a subset of Ph-like-BCP-ALL.