ArticleBlood advances2026
Genome-wide copy number profiling enhances risk stratification in multiple myeloma by shallow whole-genome sequencing.
Article in Blood advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
abstractComprehensive detection of copy number aberrations (CNAs) is critical for precise prognostic risk stratification in multiple myeloma (MM), yet 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 patients with MM across 3 hospitals and compared LeukoPrint with karyotyping and fluorescence in situ hybridization (FISH) to evaluate its diagnostic performance and clinical utility in prognostic assessment. Compared with karyotyping, LeukoPrint demonstrated a significantly higher 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 with FISH results into the Mayo Stratification for Myeloma and Risk-Adapted Therapy risk model reclassified 11.5% of standard-risk patients as high-risk, identifying candidates for intensified therapy. Furthermore, LeukoPrint genome-wide profiling revealed distinct CNA patterns between hyperdiploid and nonhyperdiploid MM, informing biological heterogeneity. LeukoPrint significantly outperforms conventional karyotyping and closely matches FISH for critical CNA markers, offering an alternative for cytogenetic profiling and prognostic risk stratification in MM.
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