The role of 1q abnormalities in multiple myeloma: Genomic insights, clinical implications, and therapeutic challenges

Chromosome 1q copy number variations, collectively termed + 1q, are 1 of the most common cytogenetic abnormalities in multiple myeloma. 1q abnormalities are associated with overexpression of a high-risk gene signature promoting cell proliferation, apoptosis resistance, genomic instability, and treatment resistance, and acquisition or expansion of + 1q subclones mediate disease development and relapse. While there remains significant controversy as to whether the presence of + 1q is itself an independent driver of poor prognosis or is simply a marker of other high-risk features, + 1q has recently been incorporated into multiple prognostic scoring models as a new high-risk cytogenetic abnormality. In this review, we present possible underlying genetic mechanisms of high-risk disease in + 1q myeloma, implications for subclonal development, its role in modifying the tumor microenvironment, current evidence for clinical significance in newly-diagnosed and relapsed patients, and current controversies in + 1q classification and prognostication. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.