Fluorescence in situ hybridization reveals the evolutionary biology of minor clone of gain/amp(1q) in multiple myeloma

• Published in: Leukemia 2024-06, Vol.38 (6), p.1299-1306
• Main Authors: Cui, Jian, Liu, Yuntong, Lv, Rui, Yan, Wenqiang, Xu, Jingyu, Li, Lingna, Du, Chenxing, Yu, Tengteng, Zhang, Shuaishuai, Deng, Shuhui, Sui, Weiwei, Hao, Mu, Yi, Shuhua, Zou, Dehui, Qiu, Lugui, Xu, Yan, An, Gang
• Format: Article
• Language: English
• Subjects: 14/32; 692/420/2489/1381; 692/499; Adult; Aged; Aged, 80 and over; Amplification; Cancer Research; Chromosomal Instability; Chromosome Aberrations; Chromosomes, Human, Pair 1 - genetics; Clonal Evolution - genetics; Critical Care Medicine; Developmental biology; Diagnosis; Disease Progression; Female; Fluorescence; Fluorescence in situ hybridization; Genomic instability; Hematology; Humans; Hybridization; In Situ Hybridization, Fluorescence - methods; Intensive; Internal Medicine; Male; Medicine; Medicine & Public Health; Middle Aged; Multiple myeloma; Multiple Myeloma - genetics; Multiple Myeloma - mortality; Multiple Myeloma - pathology; Oncology; Pathogenesis; Prognosis; Survival
• ISSN: 0887-6924; 1476-5551; 1476-5551
• DOI: 10.1038/s41375-024-02237-3

Growing evidence suggests that gain or amplification [gain/amp(1q)] accumulates during disease progression of multiple myeloma (MM). Previous investigations have indicated that small gain/amp(1q) subclones present at the time of diagnosis may evolve into dominant clones upon MM relapse. However, the influence of a minor clone of gain/amp(1q) on MM survival, as well as the correlation between different clonal sizes of gain/amp(1q) and the chromosomal instability (CIN) of MM, remains poorly understood. In this study, we analyzed fluorescence in situ hybridization (FISH) results of 998 newly diagnosed MM (NDMM) patients. 513 patients were detected with gain/amp(1q) at diagnosis. Among these 513 patients, 55 had a minor clone (≤20%) of gain/amp(1q). Patients with a minor clone of gain/amp(1q) displayed similar survival outcomes compared to those without gain/amp(1q). Further analysis demonstrated patients with a minor clone of gain/amp(1q) exhibited a clonal architecture similar to those without gain/amp(1q). Lastly, our results showed a significant increase in the clonal size of the minor clone of gain/amp(1q), frequently observed in MM. These findings suggested that a minor clone of gain/amp(1q) might represent an earlier stage in the pathogenesis of gain/amp(1q) and propose a “two-step” process in the clonal size changes of gain/amp(1q) in MM.