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.[1]
- Immune deficiency may occur in chronic lymphocytic leukemia as the majority of cases develop hypogammaglobulinemia.[2]
- 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.[1]
- 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.[3]
- Genes involved in the pathogenesis of chronic lymphocytic leukemia include:[1][3]
- Chromosome 13q deletion (most common genetic mutation)
- Chromosome 17p deletion
- Chromosome 11q deletion
- Trisomy 12
- Specific genetic mutations recently discovered to contribute for 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 macrophage and T cells provide important stimuli for the malignant proliferation of B cells in chronic lymphocytic leukemia.
- Survival of CLL cells strictly depends on a permissive microenvironment composed of cellular components like macrophages, T cells, or stromal follicular dendritic cells [20-22] providing stimuli for activation of crucial survival and pro-proliferative signaling pathways in transformed cells. This microenvironment produces various essential proteins (chemokines, cytokines, and angiogenic factors) that interact with leukemic cells via appropriate surface receptors or adhesion molecules to support the survival of CLL cells [10, 22, 23].
- ↑ 1.0 1.1 1.2 Chronic Lymphocytic Leukemia (2015) https://en.wikipedia.org/wiki/B-cell_chronic_lymphocytic_leukemia Accessed on October 12, 2015
- ↑ Nabhan C, Rosen ST (2014). "Chronic lymphocytic leukemia: a clinical review". JAMA. 312 (21): 2265–76. doi:10.1001/jama.2014.14553. PMID 25461996.
- ↑ 3.0 3.1 Hallek M (2015). "Chronic lymphocytic leukemia: 2015 Update on diagnosis, risk stratification, and treatment". Am J Hematol. 90 (5): 446–60. doi:10.1002/ajh.23979. PMID 25908509.