Pleyer Lisa, Egle Alexander, Hartmann Tanja Nicole, Greil Richard
Laboratory for Immunological and Molecular Cancer Research and IIIrd Medical Department with Hematology, Medical Oncology, Hemostaseology, Rheumatology and Infectiology, Paracelsus Medical University Salzburg, Salzburg, Austria.
Nat Rev Clin Oncol. 2009 Jul;6(7):405-18. doi: 10.1038/nrclinonc.2009.72. Epub 2009 Jun 2.
The mainstay of therapy of chronic lymphocytic leukemia (CLL) is cytotoxic chemotherapy; however, CLL is still an incurable disease with resistance to therapy developing in the majority of patients. In recent years, our understanding of the biological basis of CLL pathogenesis has substantially improved and novel treatment strategies are emerging. Tailoring and individualizing therapy according to the molecular and cellular biology of the disease is on the horizon, and advances with targeted agents such as monoclonal antibodies combined with traditional chemotherapy have lead to improved remission rates. The proposed key role of the B-cell receptor (BCR) in CLL pathogenesis has led to a number of possible opportunities for therapeutic exploitation. We are beginning to understand that the microenvironment is of utmost importance in CLL because certain T-cell subsets and stromal cells support the outgrowth and development of the malignant clone. Furthermore, an increase in our understanding of the deregulated cell-death machinery in CLL is a prerequisite to developing new targeted strategies that might be more effective in engaging with the cell-death machinery. This Review summarizes the progress made in understanding these features of CLL biology and describes novel treatment strategies that have also been exploited in current clinical trials.
慢性淋巴细胞白血病（CLL）治疗的主要方法是细胞毒性化疗；然而，CLL仍然是一种无法治愈的疾病，大多数患者会产生治疗耐药性。近年来，我们对CLL发病机制的生物学基础的理解有了显著提高，新的治疗策略不断涌现。根据疾病的分子和细胞生物学特性定制和个体化治疗即将实现，单克隆抗体等靶向药物与传统化疗联合应用取得的进展提高了缓解率。B细胞受体（BCR）在CLL发病机制中所提出的关键作用带来了许多治疗开发的可能机会。我们开始认识到微环境在CLL中至关重要，因为某些T细胞亚群和基质细胞支持恶性克隆的生长和发展。此外，深入了解CLL中失调的细胞死亡机制是开发可能更有效地作用于细胞死亡机制的新靶向策略的先决条件。本综述总结了在理解CLL生物学这些特征方面取得的进展，并描述了目前临床试验中也已采用的新治疗策略。
