Chronic lymphocytic leukemia, biology, new diagnosis and treatment

Chronic lymphocytic leukemia (CLL) is a malignancy of B CD5+cells and is the most common type of leukemia in adults. The disease is more common in men over 50 years in western countries. CLL is associated with defective apoptosis in B cells. CLL was traditionally regarded as a disease that occurs before naïve B cells meet the antigen in the lymph nodes. Laboratory diagnosis requires white blood cell count, blood smear and immunophenotyping of lymphoid cells by flow cytometry. The disease most often associated with the accumulation of CD5+ CD19+ and CD23+ B cell with reduced number of surface membrane immunoglobulin in peripheral blood, bone marrow, and lymph nodes. Clinical progression of CLL is heterogeneous, some patients need treatment immediately after diagnosis, and others do not require treatment for many years after diagnosis. Over the past decades, considerable effort has been made to understanding the molecular mechanisms underlying the heterogeneous clinical course of the disease and finding prognostic markers for clinical classification. Patients with advanced Binet or Rai stages of disease require treatment. In addition to the interactions that exist between CLL cells, number of non-tumor cell types such as bone marrow stromal cells (BMSCs), nurse like cells (NLCs), follicular dendritic cells (FDCs), T cells, and some cytokines like IL-4 in tumor microenvironment play an important role in the CLL pathogenesis. Various factors including: IGVH mutation status, genetic variation, patient age and presence of other disorders are important for disease management and the type of treatment. CLL patients carrying p53 pathway dysfunction have poor prognosis and poor responses to therapy and very short survival. Available treatments include chemotherapy, chemoimmunotherapy, or drugs targeting B cell receptor signaling, Bruton's tyrosine kinase (BTK) or inhibitors of apoptosis, such as BCL2 and new class of small molecules. Understanding the CLL biology is important in identifying high-risk patients as well as the drug and relevant therapeutic methods for better management of patients. In this review paper, the microenvironment and genetic abnormalities in the CLL as well as new diagnostic and therapeutic approaches based on the new understanding of molecular biology of CLL are discussed.