Division of Hematological Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02115, USA.
Nat Rev Clin Oncol. 2018 Apr;15(4):219-233. doi: 10.1038/nrclinonc.2017.197. Epub 2018 Jan 9.
Several haematological malignancies, including multiple myeloma (MM) and acute myeloid leukaemia (AML), have well-defined precursor states that precede the development of overt cancer. MM is almost always preceded by monoclonal gammopathy of undetermined significance (MGUS), and at least a quarter of all patients with myelodysplastic syndromes (MDS) have disease that evolves into AML. In turn, MDS are frequently anteceded by clonal haematopoiesis of indeterminate potential (CHIP). The acquisition of additional genetic and epigenetic alterations over time clearly influences the increasingly unstable and aggressive behaviour of neoplastic haematopoietic clones; however, perturbations in the bone-marrow microenvironment are increasingly recognized to have key roles in initiating and supporting oncogenesis. In this Review, we focus on the concept that the haematopoietic neoplasia-microenvironment relationship is an intimate rapport between two partners, provide an overview of the evidence supporting a role for the bone-marrow niche in promoting neoplasia, and discuss the potential for niche-specific therapeutic targets.
几种血液系统恶性肿瘤，包括多发性骨髓瘤（MM）和急性髓系白血病（AML），都有明确的前驱状态，先于明显癌症的发生。MM 几乎总是以前兆性意义未明的单克隆丙种球蛋白血症（MGUS）为前驱，至少四分之一的骨髓增生异常综合征（MDS）患者的疾病会演变为 AML。反过来，MDS 常常以前兆性不确定潜能的克隆性造血（CHIP）为前驱。随着时间的推移，获得额外的遗传和表观遗传改变显然会影响肿瘤性造血克隆越来越不稳定和侵袭性的行为；然而，骨髓微环境的紊乱越来越被认为在启动和支持肿瘤发生中具有关键作用。在这篇综述中，我们关注造血肿瘤-微环境关系是两个伙伴之间的密切关系这一概念，概述支持骨髓龛在促进肿瘤发生中作用的证据，并讨论针对龛位的特定治疗靶点的潜力。
