Ayoub Marianne, Susin Santos A, Bauvois Brigitte
Centre de Recherche des Cordeliers, Sorbonne Université, Université Paris Cité, Inserm UMRS 1138, Drug Resistance in Hematological Malignancies Team, F-75006 Paris, France.
Cancers (Basel). 2024 Dec 29;17(1):72. doi: 10.3390/cancers17010072.
Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of neoplastic CD5/CD19 B lymphocytes in the blood. These cells migrate to and proliferate in the bone marrow and lymphoid tissues. Despite the development of new therapies for CLL, drug resistance and disease relapse still occur; novel treatment approaches are therefore still needed. Inhibition of the angiogenesis involved in the progression of CLL might be a relevant therapeutic strategy. The literature data indicate that vascular endothelial growth factor, angiopoietin-2, and matrix metalloproteinase-9 are pro-angiogenic factors in CLL. A number of other CLL factors might have pro-angiogenic activity: fibroblast growth factor-2, certain chemokines (such as CXCL-12 and CXCL-2), tumor necrosis factor-α, insulin-like growth factor-1, neutrophil gelatinase-associated lipocalin, and progranulin. All these molecules contribute to the survival, proliferation, and migration of CLL cells. Here, we review the literature on these factors' respective expression profiles and roles in CLL. We also summarize the main results of preclinical and clinical trials of novel agents targeting most of these molecules in a CLL setting. Through the eradication of leukemic cells and the inhibition of angiogenesis, these therapeutic approaches might alter the course of CLL.
慢性淋巴细胞白血病（CLL）的特征是血液中肿瘤性CD5/CD19 B淋巴细胞积聚。这些细胞迁移至骨髓和淋巴组织并在其中增殖。尽管针对CLL开发了新的疗法，但耐药性和疾病复发仍然存在；因此仍需要新的治疗方法。抑制参与CLL进展的血管生成可能是一种相关的治疗策略。文献数据表明，血管内皮生长因子、血管生成素-2和基质金属蛋白酶-9是CLL中的促血管生成因子。许多其他CLL因子可能具有促血管生成活性：成纤维细胞生长因子-2、某些趋化因子（如CXCL-12和CXCL-2）、肿瘤坏死因子-α、胰岛素样生长因子-1、中性粒细胞明胶酶相关脂质运载蛋白和前颗粒蛋白。所有这些分子都有助于CLL细胞的存活、增殖和迁移。在此，我们综述了关于这些因子在CLL中的各自表达谱和作用的文献。我们还总结了在CLL背景下针对这些分子中大多数的新型药物的临床前和临床试验的主要结果。通过根除白血病细胞和抑制血管生成，这些治疗方法可能会改变CLL的病程。
