Multiple myeloma in the marrow: pathogenesis and treatments.
Multiple myeloma in the marrow: pathogenesis and treatments.
复制标题
DOI：
10.1111/nyas.13038
复制
发表时间：
2016-01
影响因子：
5.2
通讯作者：
Reagan MR
中科院分区：
文献类型：
--
作者：
Fairfield H;Falank C;Avery L;Reagan MR
多发性骨髓瘤（MM）是一种B细胞恶性肿瘤，可导致溶骨性病变和骨折。在疾病状态下，骨愈合是有限的，这是由于骨细胞增加和成骨细胞活性降低，以及MM诱导的前向反馈循环，其中骨包埋生长因子进一步增强肿瘤进展，因为骨被再吸收。MM肿瘤体细胞突变的最新研究提供了与该疾病相关的细胞遗传学变化的见解;由于MM肿瘤细胞固有的复杂性和大量突变，导致MM的起始驱动突变是多样的。这篇手稿通过总结与MM相关的癌基因和肿瘤抑制因子相关的细胞遗传学变化，审查风险因素，并描述从MGUS到明显MM的疾病进展，概述了MM发病机制。它还强调了骨髓微环境（BMM）在MM建立和进展中的重要性，以及相关的MM诱导的骨病，以及骨髓与当前和未来疗法的关系。这篇综述强调了为什么了解健康和患病BMM的基本生物学对于寻求更好的治疗和治疗遗传多样性疾病（如MM）至关重要。
Multiple myeloma (MM) is a B-cell malignancy resulting in osteolytic lesions and fractures. In the disease state, bone healing is limited due to increased osteoclastic and decreased osteoblastic activity, as well as an MM-induced forward-feedback cycle where bone-embedded growth factors further enhance tumor progression as bone is resorbed. Recent work on somatic mutation in MM tumors has provided insight into cytogenetic changes associated with this disease; the initiating driver mutations causing MM are diverse due to the complexity and multitude of mutations inherent in MM tumor cells. This manuscript provides an overview of MM pathogenesis by summarizing cytogenic changes related to oncogenes and tumor suppressors associated with MM, reviewing risk factors, and describing the disease progression from MGUS to overt MM. It also highlights the importance of the bone marrow microenvironment (BMM) in the establishment and progression of MM, as well as associated MM-induced bone disease, and the relationship of the bone marrow to current and future therapeutics. This review highlights why understanding the basic biology of the healthy and diseased BMM is crucial in the quest for better treatments and work toward a cure for genetically diverse diseases such as MM.