Department of Cytobiochemistry, Universtity of Lodz, 141/143 Pomorska Str., 90-236 Lodz, Poland.
Curr Med Chem. 2012;19(30):5109-15. doi: 10.2174/092986712803530566.
Chronic lymphocytic leukemia (CLL) is a common adult leukemia in the Western world with an incidence of 4.2/100,000/year. The clinical course of disease is highly heterogenous; it affects people over 65-70 years of age. This hematologic cancer is characterized by the resistance to apoptosis stimuli predominantly associated with overexpression of antiapoptotic Bcl-2 family members. Therapeutic options for advanced CLL patients are limited. Thus there is an urgent need to discover a novel, less toxic, and much more effective agent(s) or drug combinations for CLL patients. Among chemotherapeutic(s) and immunotherapeutics currently in use, several enzyme inhibitors were tested to gain better results in CLL treatment. Here, we review the main achievements made on targeting of prosurvival Bcl-2 proteins through the use of different approaches, i.e. anti-sense methodology, small molecules that mimic the action of BH3 domain and microRNAs (mainly miRNA-15a and miRNA-16-1).
慢性淋巴细胞白血病（CLL）是西方世界常见的成人白血病，年发病率为 4.2/100000。疾病的临床过程高度异质；它影响 65-70 岁以上的人群。这种血液系统癌症的特征是对凋亡刺激的抵抗力主要与抗凋亡 Bcl-2 家族成员的过度表达有关。晚期 CLL 患者的治疗选择有限。因此，迫切需要为 CLL 患者发现一种新型、毒性更小、更有效的药物（或药物组合）。在目前使用的化疗药物和免疫疗法中，已经测试了几种酶抑制剂，以在 CLL 治疗中获得更好的效果。在这里，我们回顾了通过使用不同方法靶向生存 Bcl-2 蛋白所取得的主要成就，即反义方法、模拟 BH3 结构域作用的小分子和 microRNAs（主要是 miRNA-15a 和 miRNA-16-1）。
