Figure 4.

Multiple myeloma (MM) subpopulation gene-set exhibits osteolytic features and is detrimental to OS. A, Through the disease course for patient #1093, spikes in serum calcium occurred during periods of disease activity with high levels of LCE-MM. B, The GEP70 score for high-risk MM was significantly higher in the LCE-MM subpopulation compared with the IGH-MM subpopulation. C, Five key genes in the GEP70 score were even more upregulated in LCE-MM compared with IGH-MM. D, In the MMRF cohort, 325 patients had RNA-seq and osteolytic data at diagnosis, with 83 showing high LCE-MM gene-set scores and 79 showing low LCE-MM gene-set scores by gene-set enrichment analysis. E, In the GSE24080 cohort, 254 microarray samples were available from patients at diagnosis, with gene-set enrichment identifying 57 new diagnosis samples with high and 62 samples with low LCE-MM gene-set scores. F, Most of the samples in the MMRF dataset that were enriched for the LCE-MM signature had ≥3 osteolytic lesions (*, P < 0.05; **, P < 0.01; ***, P < 0.001 by the Fisher exact test). G, LCE-MM enriched samples in the MMRF developed diffuse osteolytic lesions at a more rapid rate than those with a low LCE-MM signature (P = 4.9 × 10⁻³ by Cox-p test). H, Samples in the GSE24080 dataset that were enriched for the LCE-MM gene-set had increased lytic bone lesions relative to samples with a low LCE-MM gene-set score (P < 0.05 by t test). I, In the MMRF dataset patients with high LCE-MM gene enrichment score had worse OS than those with low LCE-MM gene enrichment. J, In the GSE24080 dataset patients with high LCE-MM gene enrichment score also had worse OS than those with low LCE-MM gene enrichment (log-rank test). Dotted lines indicated 50% survival.