全ゲノムコピー数プロファイリングは、浅い全ゲノムシーケンシングによる多発性骨髄腫のリスク層別化を強化する

Comprehensive detection of copy number aberrations (CNAs) is critical for precise prognostic risk stratification in multiple myeloma (MM), but conventional cytogenetic methods remain limited. We developed LeukoPrint, a shallow whole-genome sequencing (sWGS) assay for genome-wide CNA profiling. Using this platform, we analyzed CNA profiles of 423 MM patients from three hospitals, comparing LeukoPrint with karyotyping and fluorescence in situ hybridization (FISH) to evaluate its diagnostic performance and clinical utility in prognostic assessment. Compared to karyotyping, LeukoPrint significantly increased abnormality detection rate (75.2% vs 11.2%) and identified CNAs in 73.3% of karyotyping-negative cases. Concordance with FISH for key prognostic CNAs (amp(1q), del(1p), del(13q), del(17p)) was 94.0%. Based on these findings, we propose replacing karyotyping with LeukoPrint combined with FISH for routine diagnostics. Integrating LeukoPrint + FISH results into the Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) risk model reclassified 11.5% of standard-risk patients as high-risk, identifying candidates for intensified therapy. Furthermore, LeukoPrint genome-wide profiling further revealed distinct CNA patterns between hyperdiploidy and non-hyperdiploidy, informing biological heterogeneity. In conclusion, LeukoPrint significantly outperforms conventional karyotyping and closely matches FISH for crucial CNA markers, offering an alternative for cytogenetic profiling and prognostic stratification in MM.