Overview of 1q abnormalities in multiple myeloma: scientific opinions from Italian experts.

Abstract

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.