Pilot evaluation of optical genome mapping in chronic lymphocytic leukemia: complementing FISH analysis.

[BACKGROUND] The clinical heterogeneity observed in chronic lymphocytic leukemia (CLL) is largely attributed to diverse underlying genomic alterations. Fluorescence in situ hybridization (FISH) remains the standard cytogenetic technique but is limited to predefined loci. As a genome-wide approach, optical genome mapping (OGM) facilitates the identification of structural variants (SVs), such as copy number variations (CNVs), offering a broader genomic perspective. This study was designed to compare the findings of FISH and OGM in a cohort of CLL patients. By integrating these two cytogenetic approaches, we sought to evaluate the potential of OGM in detecting additional or cryptic genomic alterations that may impact prognosis and therapeutic decision-making.

[METHODS] Twenty newly diagnosed or treatment-naive CLL patients were analyzed using both FISH and OGM. SVs, CNVs, and chromosomal abnormalities were compared across methods. Concordance and discordance were evaluated, and OGM-specific alterations were examined for clinical relevance. Statistical analysis was performed using IBM SPSS Statistics for Windows, Version 26.0. Given the limited sample size (n=20), only descriptive statistics were applied. Frequencies and percentages were used to summarize categorical variables, while continuous variables were expressed as median and range.

[RESULTS] The cohort had a median age of 61.5 years (range: 44-83), with 60% male. No abnormalities were detected by either method in 2 patients. Among the remaining 18 patients OGM revealed 22 SVs, 32 CNVs, and 8 aneuploidies. In 3 patients, FISH results were negative, whereas OGM identified various abnormalities.

[CONCLUSIONS] According to our results OGM identified additional chromosomal abnormalities not covered by the FISH panel in three of our patient cohort out of the five patients in whom FISH analysis had not detected any abnormalities, highlighting the potential to reshape prognostic algorithms in CLL. Our data emphasize the utility of OGM as a valuable adjunct to standard cytogenetic assessment.