CCN2, formerly termed Connective Tissue Growth Factor, is a protein belonging to the Cellular Communication Network (CCN)-family of secreted extracellular matrix-associated proteins. As a matricellular protein it is mainly considered to be active as a modifier of signaling activity of several different signaling pathways and as an orchestrator of their cross-talk. Furthermore, CCN2 and its fragments have been implicated in the regulation of a multitude of biological processes, including cell proliferation, differentiation, adhesion, migration, cell survival, apoptosis and the production of extracellular matrix products, as well as in more complex processes such as embryonic development, angiogenesis, chondrogenesis, osteogenesis, fibrosis, mechanotransduction and inflammation. Its function is complex and context dependent, depending on cell type, state of differentiation and microenvironmental context. CCN2 plays a role in many diseases, especially those associated with fibrosis, but has also been implicated in many different forms of cancer. In the bone marrow (BM), CCN2 is highly expressed in mesenchymal stem/stromal cells (MSCs). CCN2 is important for MSC function, supporting its proliferation, migration and differentiation. In addition, stromal CCN2 supports the maintenance and longtime survival of hematopoietic stem cells, and in the presence of interleukin 7, stimulates the differentiation of pro-B lymphocytes into pre-B lymphocytes. Overexpression of CCN2 is seen in the majority of B-acute lymphoblastic leukemias, especially in certain cytogenetic subgroups associated with poor outcome. In acute myeloid leukemia, CCN2 expression is increased in MSCs, which has been associated with leukemic engraftment in vivo. In this review, the complex function of CCN2 in the BM microenvironment and in normal as well as malignant hematopoiesis is discussed. In addition, an overview is given of data on the remaining CCN family members regarding normal and malignant hematopoiesis, having many similarities and some differences in their function.

CCN2，以前称为结缔组织生长因子，是一种分泌的细胞外基质相关蛋白，属于细胞通讯网络（CCN）家族的蛋白。作为基质细胞蛋白，它主要被视为具有激活多种不同信号通路信号传导活性的作用，并作为其串扰的协调器。此外，CCN2及其片段已参与多种生物学过程的调控，包括细胞增殖，分化，粘附，迁移，细胞存活，细胞凋亡和细胞外基质产物的产生，以及更复杂的过程，例如胚胎发育，血管生成，软骨形成，成骨，纤维化，机械传导和炎症。其功能复杂且取决于上下文，具体取决于单元格类型，分化状态和微环境环境。CCN2在许多疾病（尤其是与纤维化相关的疾病）中起作用，但也与许多不同形式的癌症有关。在骨髓（BM）中，CCN2在间充质干/基质细胞（MSC）中高度表达。CCN2对于MSC功能很重要，支持其增殖，迁移和分化。另外，基质CCN2支持造血干细胞的维持和长期存活，并且在白介素7的存在下，刺激pro-B淋巴细胞分化为pre-B淋巴细胞。在大多数B急性淋巴细胞白血病中，尤其是在某些与不良预后相关的细胞遗传学亚群中，都可以看到CCN2的过表达。在急性髓细胞性白血病中，MSCs中CCN2表达增加，这与体内白血病植入有关。在这篇综述中，讨论了CCN2在BM微环境以及正常和恶性造血中的复杂功能。另外，概述了其余的CCN家族成员有关正常和恶性造血功能的数据，它们在功能上有许多相似之处和不同之处。