Figure 2.

A GEP-based 70-gene score can define high-risk myeloma. (a) Heat map of the 70 genes illustrate remarkably similar expression patterns in CD138⁺ selected tumor cells among 351 newly diagnosed patients. Red bars above the patient columns denote patients with disease-related deaths at the time of analysis. The 51 genes in rows designated by the red bar on the left (top rows; upregulated) identified patients in the upper quartile of expression at high risk for early disease-related death. The 19 gene rows designated by the green bar (downregulated), identified patients in the lower quartile of expression at high risk of early disease-related death. (b) Frequencies of the risk score defined as the log₂ geometric mean ratio of the 51 quartile 4 genes and 19 quartile 1 genes. This self-normalizing expression ratio has a marked bimodal distribution, consistent with the upper/lower quartile log-rank differential expression analysis, which was designed to detect genes that define a single high-risk group (13.1%) with an extreme expression distribution. Interpreted as an up/downregulation ratio on the log₂-scale, higher values are associated with poor outcome. The vertical line shows the high-risk versus low-risk cutoff for the log₂-scale ratio determined by K-means clustering: the percentage of samples below and above the cutoff is also shown. Kaplan–Meier estimates of EFS (c) and OS (d) in low-risk myeloma (green) and high-risk myeloma (red) showed inferior 5-year actuarial probabilities of EFS (18% versus 60%, P<0.001; HR = 4.51) and OS (28% versus 78%, P <0.001; HR=5.16) in the 13.1% patients with a high-risk signature. Reproduced with Permission from Blood.