文章：

骨髓活检在浆细胞疾病患者中的作用：是否所有存在单克隆蛋白的患者都应进行活检？

The role of bone marrow biopsy in patients with plasma cell disorders: should all patients with a monoclonal protein be biopsied?

原文发布日期：2020-05-06

DOI: 10.1038/s41408-020-0319-0

类型: Article

开放获取: 是

英文摘要：

We conducted a retrospective review of multiple myeloma (MM), smoldering multiple myeloma (SMM), and monoclonal gammopathy of undetermined significance (MGUS) patients seen at Mayo Clinic to determine whether a bone marrow biopsy (BM) is necessary in all patients diagnosed with a monoclonal protein. A total of 2254 MM, 397 SMM, and 5836 MGUS patients were included in the study. A total of 29 (1.3%) MM patients “without CRAB/FLC” were identified where BM or advanced imaging was critical for diagnosis, 8 (0.3% MM cohort) of whom were diagnosed with MM solely on BM findings (plasma cells > 60%). Without BM or advanced imaging none of these patients would be classified low-risk MGUS. A total of 314 (79%) MGUS-like SMM patients were identified where classification of SMM was based on BM findings. Without BM 97 would be classified as low/low-intermediate-risk MGUS and 151 intermediate or high-risk MGUS; 66 had missing information precluding classification. Only three (<1% SMM cohort) were low-risk MGUS without abnormalities in hemoglobin, calcium, and renal function. In patients presenting with low-risk MGUS and normal hemoglobin, calcium, and renal function, the risk of missing a diagnosis of SMM and MM by omitting BM is <1%. BM should be deferred in these patients in preference to clinical and laboratory monitoring.
 

摘要翻译： 

急性髓系白血病（AML）是一种侵袭性血液恶性肿瘤。尽管已有新兴药物问世，但总体预后仍然较差，需要新的治疗方法。PP2A磷酸酶是细胞稳态的关键调节因子，在AML中反复失活。几种PP2A激活药物（如FTY720）的抗癌活性取决于它们与SET癌蛋白的相互作用，SET是一种内源性PP2A抑制剂，在30%的AML病例中过度表达。因此，阐明SET调控机制可能为SET过表达的AML提供新的靶向治疗。在此，我们发现蛋白激酶p38β的上调是AML的常见事件。我们证明p38β通过两种机制增强SET介导的PP2A失活：通过CK2磷酸化促进SET细胞质转运，以及直接结合并稳定SET蛋白。我们在患者原代AML细胞和斑马鱼异种移植模型中证明了这一新调控机制的重要性。因此，将CK2抑制剂CX-4945（使SET保留在细胞核内）与FTY720（破坏细胞质中SET-PP2A结合）联用，可显著降低AML细胞的活力和迁移能力。总之，我们证明p38β/CK2/SET轴代表了SET依赖性PP2A失活的AML患者中一条新的潜在治疗通路。

原文链接：

The role of bone marrow biopsy in patients with plasma cell disorders: should all patients with a monoclonal protein be biopsied?