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==Pathogenesis== | ==Pathogenesis== | ||
* Chronic lymphocytic leukemia arises from pre-follicular center B cells, that are normally involved in the process of human immunoglobulins production. | * Chronic lymphocytic leukemia arises from pre-follicular center B cells, that are normally involved in the process of human immunoglobulins production. | ||
* Malignant lymphocytic cells | * Malignant lymphocytic cells infiltrate 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.<ref name="wiki">Chronic Lymphocytic Leukemia (2015) https://en.wikipedia.org/wiki/B-cell_chronic_lymphocytic_leukemia Accessed on October 12, 2015</ref> | * Chronic lymphocytic leukemia may also infiltrate the lymph nodes, spleen, and liver.<ref name="wiki">Chronic Lymphocytic Leukemia (2015) https://en.wikipedia.org/wiki/B-cell_chronic_lymphocytic_leukemia Accessed on October 12, 2015</ref> | ||
* Immune deficiency may occur in chronic lymphocytic leukemia as the majority of cases develop hypogammaglobulinemia.<ref name="pmid25461996">{{cite journal| author=Nabhan C, Rosen ST| title=Chronic lymphocytic leukemia: a clinical review. | journal=JAMA | year= 2014 | volume= 312 | issue= 21 | pages= 2265-76 | pmid=25461996 | doi=10.1001/jama.2014.14553 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25461996 }} </ref> | * Immune deficiency may occur in chronic lymphocytic leukemia as the majority of cases develop hypogammaglobulinemia.<ref name="pmid25461996">{{cite journal| author=Nabhan C, Rosen ST| title=Chronic lymphocytic leukemia: a clinical review. | journal=JAMA | year= 2014 | volume= 312 | issue= 21 | pages= 2265-76 | pmid=25461996 | doi=10.1001/jama.2014.14553 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25461996 }} </ref> | ||
Revision as of 17:42, 13 October 2015
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 infiltrate 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]
- Structural genomic aberrations 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
- Somatic gene mutations involved in the pathogenesis of chronic lymphocytic leukemia include:[3]
- 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 the malignant B cells proliferation in chronic lymphocytic leukemia.
Microscopic Pathology
- On microscopic histopathological analysis characteristic findings of chronic lymphocytic leukemia include:
- Small lymphoid cells
- Narrow cytoplasmic border
- Dense nucleus
- Lack of nucleoli
- Clumped chromatin aggregates
- Smudge cells
- Gumprecht nuclear shadows
- Shown below is a series of microscopic images seen in multiple myeloma:
- ↑ 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 3.2 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.