Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Policlinico G.B. Rossi, Piazzale L. A. Scuro 10, Verona, Italy.
Blood. 2011 Dec 15;118(25):6506-14. doi: 10.1182/blood-2011-08-376061. Epub 2011 Oct 6.
Notch signaling pathway regulates many different events of embryonic and adult development; among them, Notch plays an essential role in the onset of hematopoietic stem cells and influences multiple maturation steps of developing lymphoid and myeloid cells. Deregulation of Notch signaling determines several human disorders, including cancer. In the last decade it became evident that Notch signaling plays pivotal roles in the onset and development of T- and B-cell acute lymphoblastic leukemia by regulating the intracellular molecular pathways involved in leukemia cell survival and proliferation. On the other hand, bone marrow stromal cells are equally necessary for leukemia cell survival by preventing blast cell apoptosis and favoring their reciprocal interactions and cross-talk with bone marrow microenvironment. Quite surprisingly, the link between Notch signaling pathway and bone marrow stromal cells in acute lymphoblastic leukemia has been pointed out only recently. In fact, bone marrow stromal cells express Notch receptors and ligands, through which they can interact with and influence normal and leukemia T- and B-cell survival. Here, the data concerning the development of T- and B-cell acute lymphoblastic leukemia has been critically reviewed in light of the most recent findings on Notch signaling in stromal microenvironment.
Notch 信号通路调节胚胎和成人发育的许多不同事件；其中，Notch 在造血干细胞的起始中发挥重要作用，并影响淋巴样和髓样细胞发育的多个成熟步骤。 Notch 信号通路的失调决定了几种人类疾病，包括癌症。在过去的十年中，人们已经明显认识到 Notch 信号通路通过调节涉及白血病细胞存活和增殖的细胞内分子途径，在 T 和 B 细胞急性淋巴细胞白血病的发生和发展中发挥关键作用。另一方面，骨髓基质细胞对于白血病细胞的存活同样是必需的，因为它们可以防止成髓细胞凋亡，并促进它们与骨髓微环境的相互作用和串扰。令人惊讶的是，Notch 信号通路与急性淋巴细胞白血病中的骨髓基质细胞之间的联系直到最近才被指出。事实上，骨髓基质细胞表达 Notch 受体和配体，通过它们可以与正常和白血病 T 和 B 细胞相互作用并影响其存活。在此，根据 Notch 信号在基质微环境中的最新发现，对 T 和 B 细胞急性淋巴细胞白血病的发展进行了批判性回顾。
