hematology and oncology
Chronic Lymphocytic Leukemia (CLL)
Pathophysiology of CLL
In chronic lymphocytic leukemia, CD5+ B cells undergo malignant transformation. The B cells become continuously activated by acquisition of mutations that lead to monoclonal B-cell lymphocytosis (MBL). Further accumulation of genetic abnormalities and subsequent oncogenic transformation of monoclonal B cells leads to CLL. Lymphocytes initially accumulate in the bone marrow and then spread to lymph nodes and other lymphoid tissues, eventually inducing splenomegaly, hepatomegaly, and systemic symptoms such as fatigue, fever, night sweats, early satiety, and unintentional weight loss. As CLL progresses, abnormal hematopoiesis results in anemia, neutropenia, thrombocytopenia, and decreased immunoglobulin production. Hypogammaglobulinemia can develop in up to two thirds of patients, increasing risk for infectious complications. Patients have increased susceptibility to autoimmune hemolytic anemia (with a positive direct antiglobulin test) and autoimmune thrombocytopenia. CLL can evolve into B-cell prolymphocytic leukemia and can transform to a higher grade Non-Hodgkin Lymphomas . About 2 to 10% of CLL cases develop into diffuse large B-cell lymphoma (called Richter's transformation). 