Abstract

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 microenviroment 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.

Author affiliations

1. Laboratory for Immunological and Molecular Cancer Research and III^rd Medical Department with Hematology, Medical Oncology, Hemostaseology, Rheumatology and Infectiology, Paracelsus Medical University Salzburg, Laboratory for Immunological and Molecular Cancer Research, Salzburg, Austria.

Correspondence to: R. Greil, III^rd Medical Department with Hematology, Medical Oncology, Hemostaseology, Rheumatology and Infectiology of the Paracelsus Medical University Salzburg, Laboratory for Immunological and Molecular Cancer Research, Muellner Hauptstrasse 4B, 5020 Salzburg, Austria
Email: r.greil@salk.at

Published online 2 June 2009