Proteomic profiling revealed unique disease biology associated with 1q abnormalities in multiple myeloma.

Gain or amplification of chromosome 1q (+1q) is a common genomic alteration occurring in the plasma cells in nearly 40% of multiple myeloma patients. Although it is associated with inferior outcomes and is more common in the relapsed or refractory stages, the impact of +1q at the proteomic level remains unclear. Here, we studied enriched CD138+ plasma cells in newly diagnosed multiple myeloma to uncover molecular alterations associated with +1q. Differential expression analysis revealed significantly increased expression of over 100 proteins encoded by the 1q region, indicating a potential gene dosage effect. Pathway enrichment analysis identified enrichment of cell cycle proteins such as CDK1, MCM complex, CHEK2, PSME3 and NEK7 in cases with +1q gain. Further, protein-protein interaction network analysis showed enrichment of MYC transcriptional targets in +1q cases, including increased expression of TIPRL that is encoded on 1q24. In agreement with these findings, increased TIPRL transcript expression was correlated with +1q across different cytogenetic subgroups in the CoMMpass dataset. Further, high TIPRL expression was associated with poor prognosis in patients from the hyperdiploidy subgroup. Overall, this study highlights the role of proteomics in understanding molecular events associated with chromosomal alterations in MM and identifying potential targets for further functional analysis.