Chronic lymphocytic leukemia (CLL) is a B-cell malignancy whose progression largely depends on the lymph node and bone marrow microenvironment. Indeed, CLL cells actively proliferate in specific regions of these anatomical compartments, known as proliferation centers, while being quiescent in the blood stream. Hence, CLL cell adhesion and migration into these protective niches are critical for CLL pathophysiology. CLL cells are lodged in their microenvironment through a series of molecular interactions that are mediated by cellular adhesion molecules and their counter receptors. The importance of these adhesion molecules in the clinic is demonstrated by the correlation between the expression levels of some of them, in particular CD49d, and the prognostic likelihood. Furthermore, novel therapeutic agents, such as ibrutinib, impair the functions of these adhesion molecules, leading to an egress of CLL cells from the lymph nodes and bone marrow into the circulation together with an inhibition of homing into these survival niches, thereby preventing disease progression. Several adhesion molecules have been shown to participate in CLL adhesion and migration. Their importance also stems from the observation that they are involved in promoting, directly or indirectly, survival signals that sustain CLL proliferation and limit the efficacy of standard and novel chemotherapeutic drugs, a process known as cell adhesion-mediated drug resistance. In this respect, many studies have elucidated the molecular mechanisms underlying cell adhesion-mediated drug resistance, which have highlighted different signaling pathways that may represent potential therapeutic targets. Here, we review the role of the microenvironment and the adhesion molecules that have been shown to be important in CLL and their impact on transendothelial migration and cell-mediated drug resistance. We also discuss how novel therapeutic compounds modulate the function of this important class of molecules.
慢性淋巴细胞白血病（CLL）是一种B细胞恶性肿瘤，其进展在很大程度上依赖于淋巴结和骨髓微环境。实际上，CLL细胞在这些解剖区域的特定部位（称为增殖中心）中活跃增殖，而在血液中则处于静止状态。因此，CLL细胞的黏附和迁移进入这些保护性微环境对于CLL的病理生理学至关重要。CLL细胞通过一系列由细胞黏附分子及其对应受体介导的分子相互作用，定植于其微环境中。这些黏附分子在临床中的重要性体现在某些分子（特别是CD49d）的表达水平与预后可能性之间的相关性上。此外，新型治疗药物（如伊布替尼）会损害这些黏附分子的功能，导致CLL细胞从淋巴结和骨髓进入血液循环，同时抑制其归巢至这些生存微环境，从而阻止疾病进展。已有研究表明，多种黏附分子参与CLL细胞的黏附和迁移。其重要性还源于观察到这些分子直接或间接参与促进生存信号，这些信号维持CLL增殖并限制标准及新型化疗药物的疗效，这一过程被称为细胞黏附介导的耐药性。在这方面，许多研究阐明了细胞黏附介导耐药性的分子机制，揭示了可能成为潜在治疗靶点的不同信号通路。本文综述了微环境的作用以及在CLL中被证实具有重要意义的黏附分子，及其对跨内皮迁移和细胞介导耐药性的影响。我们还讨论了新型治疗化合物如何调节这类重要分子的功能。
The Role of the Microenvironment and Cell Adhesion Molecules in Chronic Lymphocytic Leukemia
肿瘤(癌症)患者之家