Sandbox:patho3

Pathogenesis

• Chronic lymphocytic leukemia arises from pre-follicular center B cells, that are normally involved in the process of human immunoglobulins production.
• Malignant lymphocytic cells infiltrates hematopoietic sites such as the bone marrow where they interfere with the production of normal blood cells.
• Chronic lymphocytic leukemia may also infiltrate the lymph nodes, spleen, and liver.
• Immune deficiency may occur in chronic lymphocytic leukemia as the majority of cases develop hypogammaglobulinemia.
• Warm autoimmune hemolytic anemia may develop due to the production of IgA and IgG autoantibodies among certain cases of chronic lymphocytic anemia.
• Richter's transformation may occur among 1-5% of chronic lymphocytic leukemia cases.
• Richter's transformation represents the conversion of chronic lymphocytic leukemia into a more aggressive, rapidly growing large B cell lymphoma.

Genetics

• Development of chronic lymphocytic leukemia is the result of multiple genetic mutations that promote leukemic proliferation and apoptotic resistance of mature B cells.
• Structural genomic aberrations involved in the pathogenesis of chronic lymphocytic leukemia include:

• Chromosome 13q deletion (most common genetic mutation)
• Chromosome 17p deletion
• Chromosome 11q deletion
• Trisomy 12

• Somatic gene mutations involved in the pathogenesis of chronic lymphocytic leukemia include:

• NOTCH1 gene located on chromosome 9
• MYD88 gene located on chromosome 3
• TP53 gene located on chromosome 7
• ATM gene located on chromosome 11
• SF3B1 gene located on chromosome 2
• FBXW7 gene located on chromosome 4
• CHD2 gene located on chromosome 15

• Production of cytokines, angiogenic factors, and chemokines by the surrounding macrophages and T cells provide important stimuli for malignant B cells proliferation in chronic lymphocytic leukemia.