Chronic lymphocytic leukemia pathophysiology: Difference between revisions
| Line 12: | Line 12: | ||
* [[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> | ||
* [[Warm autoimmune hemolytic anemia]] may develop due to the production of [[IgA]] and [[IgG]] [[autoantibodies]] among certain cases of chronic lymphocytic anemia. | * [[Warm autoimmune hemolytic anemia]] may develop due to the production of [[IgA]] and [[IgG]] [[autoantibodies]] among certain cases of chronic lymphocytic anemia. | ||
* Production of [[cytokine]]s, [[angiogenic]] factors, and [[chemokine]]s by the surrounding [[macrophage]]s and [[T cell]]s provide important stimuli for [[malignant]] [[B cell]]s proliferation in chronic lymphocytic leukemia. | * Production of [[cytokine]]s, [[angiogenic]] factors, and [[chemokine]]s by the surrounding [[macrophage]]s and [[T cell]]s provide important stimuli for [[malignant]] [[B cell]]s proliferation in chronic lymphocytic leukemia.<ref name="pmid25908509">{{cite journal| author=Hallek M| title=Chronic lymphocytic leukemia: 2015 Update on diagnosis, risk stratification, and treatment. | journal=Am J Hematol | year= 2015 | volume= 90 | issue= 5 | pages= 446-60 | pmid=25908509 | doi=10.1002/ajh.23979 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25908509 }} </ref> | ||
* [[Richter's transformation]] may occur among 1-5% of chronic lymphocytic leukemia cases.<ref name="wiki">Chronic Lymphocytic Leukemia (2015) https://en.wikipedia.org/wiki/B-cell_chronic_lymphocytic_leukemia Accessed on October 12, 2015</ref> | * [[Richter's transformation]] may occur among 1-5% of chronic lymphocytic leukemia cases.<ref name="wiki">Chronic Lymphocytic Leukemia (2015) https://en.wikipedia.org/wiki/B-cell_chronic_lymphocytic_leukemia Accessed on October 12, 2015</ref> | ||
* Richter's transformation represents the conversion of chronic lymphocytic leukemia into a more aggressive, rapidly growing [[large B cell lymphoma]]. | * Richter's transformation represents the conversion of chronic lymphocytic leukemia into a more aggressive, rapidly growing [[large B cell lymphoma]]. | ||
Revision as of 18:28, 13 October 2015
|
Chronic lymphocytic leukemia Microchapters |
|
Differentiating Chronic lymphocytic leukemia from other Diseases |
|---|
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
Chronic lymphocytic leukemia pathophysiology On the Web |
|
American Roentgen Ray Society Images of Chronic lymphocytic leukemia pathophysiology |
|
Directions to Hospitals Treating Chronic lymphocytic leukemia |
|
Risk calculators and risk factors for Chronic lymphocytic leukemia pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2]
Overview
Chronic lymphocytic leukemia arises from pre-follicular center B cells, that are normally involved in the process of human immunoglobulins production. Development of chronic lymphocytic leukemia is the result of multiple genetic mutations that promote both malignant leukemic proliferation and apoptotic resistance of mature B cells. Structural genetic mutations involved in the pathogenesis of chronic lymphocytic leukemia include chromosome 13q deletion, chromosome 17p deletion, and chromosome 11q deletion. On microscopic histopathological analysis characteristic findings of chronic lymphocytic leukemia include small lymphoid cells, thin cytoplasmic border, lack of nucleoli, and presence of smudge cells.[1][2][3][4]
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 red blood cells and platelets.
- 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.
- 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.[3]
- 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 both malignant leukemic proliferation and apoptotic resistance of mature B cells.[3]
- Structural genetic mutations involved in the pathogenesis of chronic lymphocytic leukemia include:[1][3]
- Chromosome 13 long arm deletion (most common genetic mutation)
- Chromosome 17 short arm deletion
- Chromosome 11 long arm deletion
- Trisomy 12
- Somatic genetic 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
Microscopic Pathology
- On microscopic histopathological analysis characteristic findings of chronic lymphocytic leukemia include:[2][3]
- On Immunohistochemistry characteristic findings of chronic lymphocytic leukemia include:[4]
- Shown below is a series of microscopic images seen in multiple myeloma:
-
![Chronic lymphocytic leukemia demonstrated on low magnification[4]](/images/9/9b/Chronic_lymphocytic_leukemia_-_low_mag.jpg)
Chronic lymphocytic leukemia demonstrated on low magnification[4]
-
![Chronic lymphocytic leukemia demonstrated on intermediate magnification[4]](/images/5/55/Chronic_lymphocytic_leukemia_-_intermed_mag.jpg)
Chronic lymphocytic leukemia demonstrated on intermediate magnification[4]
-
![Chronic lymphocytic leukemia demonstrated on high magnification[4]](/images/2/24/Chronic_lymphocytic_leukemia_-_high_mag.jpg)
Chronic lymphocytic leukemia demonstrated on high magnification[4]
-
![Chronic lymphocytic leukemia demonstrated on very high magnification[4]](/images/7/77/Chronic_lymphocytic_leukemia_-_very_high_mag.jpg)
Chronic lymphocytic leukemia demonstrated on very high magnification[4]
![Chronic lymphocytic leukemia demonstrated on low magnification[4]](/index.php/File:Chronic_lymphocytic_leukemia_-_low_mag.jpg)
![Chronic lymphocytic leukemia demonstrated on intermediate magnification[4]](/index.php/File:Chronic_lymphocytic_leukemia_-_intermed_mag.jpg)
![Chronic lymphocytic leukemia demonstrated on high magnification[4]](/index.php/File:Chronic_lymphocytic_leukemia_-_high_mag.jpg)
![Chronic lymphocytic leukemia demonstrated on very high magnification[4]](/index.php/File:Chronic_lymphocytic_leukemia_-_very_high_mag.jpg)
References
- ↑ 1.0 1.1 1.2 1.3 Chronic Lymphocytic Leukemia (2015) https://en.wikipedia.org/wiki/B-cell_chronic_lymphocytic_leukemia Accessed on October 12, 2015
- ↑ 2.0 2.1 2.2 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 3.3 3.4 3.5 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.
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 Chronic Lymphocytic Leukemia. Libre Pathology (2015) http://librepathology.org/wiki/index.php/B_cell_small_lymphocytic_lymphoma/chronic_lymphocytic_leukemia Accessed on October, 12 2015