Division of Hematology, Mayo Clinic, Rochester, MN, USA.
Department of Laboratory Medicine, Mayo Clinic, Rochester, MN, USA.
Leukemia. 2020 Oct;34(10):2749-2753. doi: 10.1038/s41375-020-0940-8. Epub 2020 Jun 27.
Our group previously demonstrated that M-protein light chain (LC) glycosylation can be detected on routine MASS-FIX testing. Glycosylation is increased in patients with immunoglobulin LC amyloidosis (AL) and rarely changes over the course of a patient's lifetime. To determine the rates of progression to AL and other plasma cell disorders (PCDs), we used residual serum samples from the Olmsted monoclonal gammopathy of undetermined significance (MGUS) screening cohort. Four-hundred and fourteen patients with known MGUS were tested by MASS-FIX, and 25 (6%) were found to have glycosylated LCs. With a median follow-up of surviving patients of 22.2 years, the 20-year progression rates to a malignant PCD were 67% (95% CI 29%, 84%) and 13% (95% CI 9%, 18%) for patients with and without glycosylated LCs, respectively. The risk of progression was independent of Mayo MGUS risk score. The respective rates of progression to AL at 20 years were 21% (95% CI 0.0%, 38%) and 3% (95% CI 0.6%, 5.5%). In summary, monoclonal LC glycosylation is a potent risk factor for progression to AL, myeloma, and other PCDs, an observation which could lead to earlier diagnoses and potentially reduced morbidity and mortality.
我们的研究小组曾展示过，M 蛋白轻链（LC）糖基化可在常规 MASS-FIX 检测中被检测到。免疫球蛋白 LC 淀粉样变性（AL）患者的糖基化程度会增加，且在患者的一生中很少发生变化。为了确定进展为 AL 和其他浆细胞疾病（PCD）的概率，我们使用了奥姆斯特德单克隆丙种球蛋白血症意义未明（MGUS）筛查队列中的剩余血清样本。对 414 例已知 MGUS 的患者进行了 MASS-FIX 检测，其中 25 例（6%）发现存在糖基化 LC。在对存活患者进行中位随访 22.2 年后，有糖基化 LC 的患者恶性 PCD 的 20 年进展率分别为 67%（95%CI 29%，84%）和 13%（95%CI 9%，18%）。进展风险独立于 Mayo MGUS 风险评分。20 年时进展为 AL 的风险分别为 21%（95%CI 0.0%，38%）和 3%（95%CI 0.6%，5.5%）。总之，单克隆 LC 糖基化是进展为 AL、骨髓瘤和其他 PCD 的强有力危险因素，这一观察结果可能导致更早的诊断，并潜在地降低发病率和死亡率。
