Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Address: 6627, Presidente Antônio Carlos Ave, Pampulha, Zip Code 31270-901, Belo Horizonte, MG, Brazil.
Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Address: 6627, Presidente Antônio Carlos Ave, Pampulha, Zip Code 31270-901, Belo Horizonte, MG, Brazil.
Biomed Pharmacother. 2018 Jan;97:349-358. doi: 10.1016/j.biopha.2017.10.105. Epub 2017 Nov 6.
Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease that affects B lymphocytes in most cases. Leukemic lymphocytes have prolonged longevity, defined by resistance to apoptosis. These cells can accumulate in peripheral blood, bone marrow, and solid lymphoid organs. CLL may be indolent or aggressive and has a range of prognostic factors such as expression of CD38 and ZAP-70, immunophenotypic and cytogenetic changes, imbalanced apoptosis proteins, and others. Although CLL has a low mortality rate, this disease is generally not considered curable until today. CLL treatment involves alkylating agents and glucocorticoids, purine analogs, monoclonal antibody therapies, and bone marrow transplantation. In recent decades, new drugs have appeared focusing on new targets and specific molecules, such as the BCR receptor, Bruton's tyrosine kinase, phosphatidylinositol 3-kinase, spleen tyrosine kinase, apoptosis proteins and microRNAs. The most appropriate treatment for CLL is one that involves in its protocol a combination of drugs according to the prognostic factors presented by each patient. In this sense, treatment individualization is essential. This article examines standard treatments for CLL and explores new treatments and potential new targets, as well as schematic protocols to understand where we are, how the treatment has evolved, and the advantages and disadvantages of new targets for CLL therapy.
慢性淋巴细胞白血病(CLL)是一种淋巴增殖性疾病,大多数情况下影响 B 淋巴细胞。白血病淋巴细胞具有延长的寿命,其特征是对细胞凋亡的抵抗。这些细胞可以在外周血、骨髓和实体淋巴器官中积聚。CLL 可能是惰性的或侵袭性的,具有一系列预后因素,如 CD38 和 ZAP-70 的表达、免疫表型和细胞遗传学变化、失衡的凋亡蛋白等。尽管 CLL 的死亡率较低,但直到今天,这种疾病通常仍被认为无法治愈。CLL 的治疗包括烷化剂和糖皮质激素、嘌呤类似物、单克隆抗体治疗和骨髓移植。近几十年来,出现了一些新的药物,这些药物的作用靶点和特定分子各不相同,如 BCR 受体、布鲁顿酪氨酸激酶、磷脂酰肌醇 3-激酶、脾酪氨酸激酶、凋亡蛋白和 microRNAs。CLL 最合适的治疗方法是根据每位患者的预后因素,在方案中组合使用药物。从这个意义上说,治疗个体化是至关重要的。本文检查了 CLL 的标准治疗方法,并探讨了新的治疗方法和潜在的新靶点,以及示意性方案,以了解我们所处的位置、治疗方法的演变以及新靶点在 CLL 治疗中的优缺点。