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.

越来越多的证据表明，增益或放大 [gain/amp(1q)] 在多发性骨髓瘤 (MM) 疾病进展过程中不断累积。先前的研究表明，诊断时存在的小增益/amp(1q)亚克隆可能在多发性骨髓瘤复发时演变成显性克隆。然而，gain/amp(1q) 的较小克隆对 MM 存活的影响，以及不同大小的 Gain/amp(1q) 克隆与 MM 染色体不稳定性 (CIN) 之间的相关性仍然知之甚少。在这项研究中，我们分析了 998 名新诊断的 MM (NDMM) 患者的荧光原位杂交 (FISH) 结果。 513 名患者在诊断时检测到增益/amp(1q)。在这 513 名患者中，55 名患者有增益/amp(1q) 的微小克隆 (≤20%)。与没有增益/amp(1q) 的患者相比，具有较小增益/amp(1q) 克隆的患者表现出相似的生存结果。进一步分析表明，具有少量增益/amp(1q) 克隆的患者表现出与没有增益/amp(1q) 的患者相似的克隆结构。最后，我们的结果显示，增益/amp(1q) 次要克隆的克隆大小显着增加，这在 MM 中经常观察到。这些发现表明，gain/amp(1q) 的较小克隆可能代表了 Gain/amp(1q) 发病机制的早期阶段，并提出了 Gain/amp(1q) 克隆大小变化的“两步”过程。在MM。