[Chronic lymphocytic leukemia: update on pathophysiology and management]

Chronic lymphocytic leukemia (CLL) is the most common hematological malignancy in the Western countries. Although a multi-step model has been proposed for the pathogenesis of CLL as well as other malignancies, the precise mechanism underlying the development of CLL remains complicated and unclear. In addition, several studies have investigated adverse prognostic factors, including gene abnormalities and the evolution of clones with the disease progression. FCR (fludarabine, cyclophosphamide, and rituximab) has been the standard first-line therapy for "fit" younger patients without TP53 abnormality/17p deletion. Patients with CLL with TP53 abnormality/17p deletion exhibit poor prognosis because of the resistance to chemoimmunotherapy such as FCR. However, several novel targeted therapies such as B-cell receptor inhibitors including Bruton's tyrosine kinase inhibitors, PI3 kinase inhibitors, and Bcl-2 antagonists have been developed and have proven effective for high-risk patients with CLL with TP53 dysfunction. Moreover, in patients with CLL with the IGHV somatic mutation, FCR therapy offers long-term disease-free survival. These promising findings suggest the possibility of a cure. Although the aim of CLL treatment has been disease control, it is gradually changing to the possibility of a cure. Furthermore, the evaluation of minimal residual disease is important for the cure of CLL.