D'Agostino Mattia, Martello Marina, De Paoli Lorenzo, Mangiacavalli Silvia, Derudas Daniele, Fazio Francesca, Furlan Anna, Liberatore Carmine, Mele Giuseppe, Mina Roberto, Ria Roberto, Zamagni Elena
Division of Hematology, Department of Molecular Biotechnology and Health Sciences, AOU Città della Salute e della Scienza di Torino, University of Torino, Torino, Italy.
IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli", Bologna, Italy.
Ann Hematol. 2025 Mar;104(3):1443-1458. doi: 10.1007/s00277-025-06212-5. Epub 2025 Feb 13.
Multiple myeloma (MM) is a haematological malignancy characterised by high genomic heterogeneity. One of the most common cytogenic abnormalities in MM is the gain of genetic material at the long arm (q) of chromosome 1 (+ 1q). While many mechanisms of resistance have been associated with + 1q alterations (e.g. CD38 downregulation, impairment of complement-dependent cytotoxicity, or induction of immunosuppression), the precise genetic or pathogenetic factors responsible for these alterations are still being investigated. Although interphase fluorescence in situ hybridisation (iFISH) is the gold standard for the detection of + 1q abnormalities used by the majority of diagnostic laboratories worldwide, there are no universally recognised cut-offs for + 1q positivity or a threshold for clinical meaningfulness. Because iFISH alone is insufficient to elucidate the extent of + 1q and other cytogenetic abnormalities in MM, sequencing-based methods could be adopted. The second revision of the international staging system for MM recently recognised + 1q as a high-risk feature. There is increasing evidence that + 1q has a prognostic value and influences the duration of remission, suggesting that patients with MM and + 1q may benefit from tailored therapy. This review comprehensively summarises the most recent biological evidence and clinical data on + 1q abnormalities in MM. However, given the heterogeneous data available, it remains difficult to draw firm conclusions. In clinical practice, +1q alterations should be evaluated along with other cytogenetic abnormalities and other biological and clinical characteristics of the disease. Ongoing and future studies will help the full understanding of the role of + 1q in MM.
多发性骨髓瘤(MM)是一种血液系统恶性肿瘤,具有高度的基因组异质性。MM最常见的细胞遗传学异常之一是1号染色体长臂(q)的遗传物质增加(+1q)。虽然许多耐药机制与+1q改变有关(如CD38下调、补体依赖性细胞毒性受损或免疫抑制诱导),但导致这些改变的确切遗传或致病因素仍在研究中。尽管间期荧光原位杂交(iFISH)是全球大多数诊断实验室用于检测+1q异常的金标准,但对于+1q阳性尚无普遍认可的临界值或临床意义阈值。由于仅iFISH不足以阐明MM中+1q和其他细胞遗传学异常的程度,因此可采用基于测序的方法。MM国际分期系统的第二次修订最近将+1q确认为高危特征。越来越多的证据表明+1q具有预后价值并影响缓解期的持续时间,这表明MM合并+1q的患者可能从量身定制的治疗中获益。本综述全面总结了MM中+1q异常的最新生物学证据和临床数据。然而,鉴于现有数据的异质性,仍然难以得出确凿的结论。在临床实践中,应将+1q改变与其他细胞遗传学异常以及该疾病的其他生物学和临床特征一起进行评估。正在进行的和未来的研究将有助于全面了解+1q在MM中的作用。