Curto-Garcia Natalia, Harrison Claire, McLornan Donal P
Department of Hematology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Department of Hematology, Guy's and St Thomas' NHS Foundation Trust, London, UK
Haematologica. 2020 May;105(5):1189-1200. doi: 10.3324/haematol.2019.243121. Epub 2020 Apr 2.
The bone marrow niche is a complex and dynamic structure composed of a multitude of cell types which functionally create an interactive network facilitating hematopoietic stem cell development and maintenance. Its specific role in the pathogenesis, response to therapy, and transformation of myeloproliferative neoplasms has only recently been explored. Niche functionality is likely affected not only by the genomic background of the myeloproliferative neoplasm-associated mutated hematopoietic stem cells, but also by disease-associated 'chronic inflammation', and subsequent adaptive and innate immune responses. 'Cross-talk' between mutated hematopoietic stem cells and multiple niche components may contribute to propagating disease progression and mediating drug resistance. In this timely article, we will review current knowledge surrounding the deregulated bone marrow niche in myeloproliferative neoplasms and suggest how this may be targeted, either directly or indirectly, potentially influencing therapeutic choices both now and in the future.
骨髓微环境是一个复杂且动态的结构,由多种细胞类型组成,这些细胞在功能上形成一个相互作用的网络,促进造血干细胞的发育和维持。其在骨髓增殖性肿瘤的发病机制、对治疗的反应及转化过程中的具体作用直到最近才被探索。微环境功能可能不仅受到骨髓增殖性肿瘤相关的突变造血干细胞的基因组背景影响,还受到疾病相关的“慢性炎症”以及随后的适应性和先天性免疫反应的影响。突变的造血干细胞与多个微环境成分之间的“相互作用”可能有助于推动疾病进展并介导耐药性。在这篇及时的文章中,我们将综述目前关于骨髓增殖性肿瘤中失调的骨髓微环境的知识,并提出如何直接或间接靶向它,这可能会影响现在及未来的治疗选择。