These observations are corroborated by functional studies that have shown that, while both CD4(+) and CD8(+) T-cells from the BM of patients with MGUS can effect vigorous tumor-specific responses, these actions are not seen with T-cells from the BM of patients with active MM.62 A potential explanation for this phenomenon is that an increasing tumor burden from MGUS to MM may result in T-cell exhaustion. This evidence concerns the gene CD4 and Miyoshi myopathy.