Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Section of Molecular Hematology and Therapy, Leukemia Department, The University of Texas MD Anderson Cancer Center, Houston, TX.
Haematologica. 2018 Dec;103(12):1945-1955. doi: 10.3324/haematol.2018.197004. Epub 2018 Oct 18.
The bone marrow microenvironment, also known as the bone marrow niche, is a complex network of cell types and acellular factors that supports normal hematopoiesis. For many years, leukemia was believed to be caused by a series of genetic hits to hematopoietic stem and progenitor cells, which transform them to preleukemic, and eventually to leukemic, cells. Recent discoveries suggest that genetic alterations in bone marrow niche cells, particularly in osteogenic cells, may also cause myeloid leukemia in mouse models. The osteogenic niche, which consists of osteoprogenitors, preosteoblasts, mature osteoblasts, osteocytes and osteoclasts, has been shown to play a critical role in the maintenance and expansion of hematopoietic stem and progenitor cells as well as in their oncogenic transformation into leukemia stem/initiating cells. We have recently shown that acute myeloid leukemia cells induce osteogenic differentiation in mesenchymal stromal cells to gain a growth advantage. In this review, we discuss the role of the osteogenic niche in the maintenance of hematopoietic stem and progenitor cells, as well as in their transformation into leukemia cells. We also discuss the signaling pathways that regulate osteogenic niche-hematopoietic stem and progenitor cells or osteogenic niche-leukemic stem/initiating cell interactions in the bone marrow, together with novel approaches for therapeutically targeting these interactions.
骨髓微环境，又称骨髓龛，是一个支持正常造血的细胞类型和无细胞因子的复杂网络。多年来，人们一直认为白血病是由一系列对造血干细胞和祖细胞的遗传打击引起的，这些打击使它们转化为白血病前细胞，最终转化为白血病细胞。最近的发现表明，骨髓龛细胞（尤其是成骨细胞）中的遗传改变也可能导致小鼠模型中的髓性白血病。成骨龛由成骨前体细胞、前成骨细胞、成熟成骨细胞、骨细胞和破骨细胞组成，它在维持和扩增造血干细胞和祖细胞方面以及在将其恶性转化为白血病干细胞/起始细胞方面发挥着关键作用。我们最近表明，急性髓系白血病细胞可诱导间充质基质细胞发生成骨分化，从而获得生长优势。在这篇综述中，我们讨论了成骨龛在维持造血干细胞和祖细胞以及将其转化为白血病细胞方面的作用。我们还讨论了调节骨髓中成骨龛-造血干细胞和祖细胞或成骨龛-白血病干细胞/起始细胞相互作用的信号通路，以及针对这些相互作用的新治疗方法。
