Chronic lymphocytic leukemia pathophysiology: Difference between revisions
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==Overview== | ==Overview== | ||
Chronic lymphocytic leukemia arises from pre-follicular center [[B cell]]s, that are normally involved in the process of human [[immunoglobulin]] | Chronic lymphocytic leukemia arises from pre-follicular center [[B cell]]s, that are normally involved in the process of human [[immunoglobulin]] production. Development of chronic lymphocytic leukemia is the result of multiple [[genetic mutation]]s that promote both [[malignant]] leukemic proliferation and [[apoptotic]] resistance of mature B cells. Structural [[genetic mutation]]s 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 [[nucleolus]], and the presence of smudge cells.<ref name="wiki">Chronic Lymphocytic Leukemia. Wikipedia (2015) https://en.wikipedia.org/wiki/B-cell_chronic_lymphocytic_leukemia Accessed on October 12, 2015</ref><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><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><ref name="patho">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</ref> | ||
==Pathogenesis== | ==Pathogenesis== | ||
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* [[Autoimmune]] [[thrombocytopenia]] may develop due to the production of [[autoantibodies]].<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> | * [[Autoimmune]] [[thrombocytopenia]] may develop due to the production of [[autoantibodies]].<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> | ||
* 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> | * 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 represents the conversion of chronic lymphocytic leukemia into a more aggressive and rapidly growing [[large B cell lymphoma]]. | |||
* [[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> | ||
==Genetics== | ==Genetics== | ||
| Line 23: | Line 23: | ||
:* [[Chromosome 13]] long arm deletion (most common genetic mutation) | :* [[Chromosome 13]] long arm deletion (most common genetic mutation) | ||
:* [[Chromosome 17]] short arm deletion | :* [[Chromosome 17]] short arm deletion | ||
:* Trisomy 12 | :* [[Trisomy]] 12 | ||
* Somatic genetic mutations involved in the pathogenesis of chronic lymphocytic leukemia include:<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> | * Somatic genetic mutations involved in the pathogenesis of chronic lymphocytic leukemia include:<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> | ||
:* ''SF3B1'' gene located on [[chromosome 2]] | :* ''SF3B1'' gene located on [[chromosome 2]] | ||
Revision as of 21:20, 29 August 2018
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Chronic lymphocytic leukemia Microchapters |
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Differentiating Chronic lymphocytic leukemia from other Diseases |
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Diagnosis |
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Chronic lymphocytic leukemia pathophysiology On the Web |
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American Roentgen Ray Society Images of Chronic lymphocytic leukemia pathophysiology |
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Directions to Hospitals Treating Chronic lymphocytic leukemia |
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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 immunoglobulin 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 nucleolus, and the 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.
- Autoimmune thrombocytopenia may develop due to the production of autoantibodies.[2]
- 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 represents the conversion of chronic lymphocytic leukemia into a more aggressive and rapidly growing large B cell lymphoma.
- Richter's transformation may occur among 1-5% of chronic lymphocytic leukemia cases.[1]
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 11 long arm deletion
- Chromosome 13 long arm deletion (most common genetic mutation)
- Chromosome 17 short arm deletion
- Trisomy 12
- Somatic genetic mutations involved in the pathogenesis of chronic lymphocytic leukemia include:[3]
- SF3B1 gene located on chromosome 2
- FBXW7 gene located on chromosome 4
- MYD88 gene located on chromosome 3
- TP53 gene located on chromosome 7
- NOTCH1 gene located on chromosome 9
- ATM gene located on chromosome 11
- CHD2 gene located on chromosome 15
- The type of the genetic mutation is considered one of the important factors that determine the optimal management protocol of chronic lymphocytic leukemia patients.[2]
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]
- Illustrated below is a series of microscopic images observed in chronic lymphocytic leukemia:
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![Chronic lymphocytic leukemia illustrated on low magnification[4]](/images/9/9b/Chronic_lymphocytic_leukemia_-_low_mag.jpg)
Chronic lymphocytic leukemia illustrated on low magnification[4]
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![Chronic lymphocytic leukemia illustrated on intermediate magnification[4]](/images/5/55/Chronic_lymphocytic_leukemia_-_intermed_mag.jpg)
Chronic lymphocytic leukemia illustrated on intermediate magnification[4]
-
![Chronic lymphocytic leukemia illustrated on high magnification[4]](/images/2/24/Chronic_lymphocytic_leukemia_-_high_mag.jpg)
Chronic lymphocytic leukemia illustrated on high magnification[4]
-
![Chronic lymphocytic leukemia illustrated on very high magnification[4]](/images/7/77/Chronic_lymphocytic_leukemia_-_very_high_mag.jpg)
Chronic lymphocytic leukemia illustrated on very high magnification[4]
![Chronic lymphocytic leukemia illustrated on low magnification[4]](/index.php/File:Chronic_lymphocytic_leukemia_-_low_mag.jpg)
![Chronic lymphocytic leukemia illustrated on intermediate magnification[4]](/index.php/File:Chronic_lymphocytic_leukemia_-_intermed_mag.jpg)
![Chronic lymphocytic leukemia illustrated on high magnification[4]](/index.php/File:Chronic_lymphocytic_leukemia_-_high_mag.jpg)
![Chronic lymphocytic leukemia illustrated 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. Wikipedia (2015) https://en.wikipedia.org/wiki/B-cell_chronic_lymphocytic_leukemia Accessed on October 12, 2015
- ↑ 2.0 2.1 2.2 2.3 2.4 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