Proteomic and transcriptomic profiling identifies TIPRL as a potential target in multiple myeloma with 1q gain

Amplification or gain 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 advanced disease stages, the impact of +1q at the proteomic level remains unclear. Here, we studied enriched CD138+ bone marrow plasma cells in newly diagnosed multiple myeloma to uncover molecular alterations associated with +1q. Differential expression analysis revealed significantly increased expression of several proteins encoded by 1q region indicating potential gene dosage effect. Pathway enrichment analysis identified enrichment of cell cycle proteins. Further, protein-protein interaction network analysis showed enrichment of MYC transcriptional targets in +1q cases, including increased expression of TIPRL (located on 1q23). In agreement with these findings, increased TIPRL transcript expression was correlated with +1q across different cytogenetic subgroups in the CoMMPass dataset. High TIPRL protein 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.