Shanafelt Tait D, Kay Neil E
Division of Hematology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Semin Oncol. 2006 Apr;33(2):174-85. doi: 10.1053/j.seminoncol.2006.01.008.
Angiogenesis has been found to be an important regulator in the growth and metastasis of solid tumors. More recent studies have also demonstrated the importance of this biologic process in normal hematopoietic cell development and the pathophysiology of several hematologic malignancies. This review provides an overview of the clinical and biologic importance of angiogenesis in chronic lymphocytic leukemia (CLL). Patients with CLL have detectable levels of both plasma and cellular pro- and anti-angiogenic cytokines, as well as abnormal neovascularization in the marrow and lymph nodes. Recent evidence suggests a vascular endothelial growth factor (VEGF)-based autocrine pathway promotes the survival of CLL B cells in part through upregulation of anti-apoptotic proteins. Additionally, interactions between CLL B cells and their microenvironment generate alterations in the secretion of angiogenic factors that result in enhanced leukemic B-cell resistance to apoptotic cell death. From a clinical standpoint, interpatient variation is observed in markers of angiogenesis and appears to have prognostic implications. Several clinical trials evaluating the efficacy of anti-angiogenic agents for treatment of patients with CLL are underway with promising preliminary results. Additional research is needed to identify the regulation of aberrant and critical angiogenic pathways in CLL B cells, to determine how angiogenic markers can be used to improve prognostication for CLL patients, and to explore how the angiogenic characteristics of CLL B cells can best be manipulated for therapeutic benefit.
血管生成已被发现是实体瘤生长和转移的重要调节因子。最近的研究还表明，这一生物学过程在正常造血细胞发育和几种血液系统恶性肿瘤的病理生理学中具有重要意义。本文综述了血管生成在慢性淋巴细胞白血病（CLL）中的临床和生物学重要性。CLL患者的血浆和细胞促血管生成及抗血管生成细胞因子水平均可检测到，骨髓和淋巴结中也存在异常的新血管形成。最近的证据表明，基于血管内皮生长因子（VEGF）的自分泌途径部分通过上调抗凋亡蛋白来促进CLL B细胞的存活。此外，CLL B细胞与其微环境之间的相互作用会导致血管生成因子分泌的改变，从而增强白血病B细胞对凋亡性细胞死亡的抗性。从临床角度来看，血管生成标志物在患者之间存在差异，并且似乎具有预后意义。几项评估抗血管生成药物治疗CLL患者疗效的临床试验正在进行中，初步结果令人鼓舞。还需要进一步研究以确定CLL B细胞中异常和关键血管生成途径的调控机制，确定血管生成标志物如何用于改善CLL患者的预后，以及探索如何最好地操控CLL B细胞的血管生成特性以获得治疗益处。
