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==Overview== | ==Overview== | ||
Hairy cell leukemia arises from [[B cell]]s, that are normally involved in the process of human [[immunoglobulin]]s production.<ref name="m">Magrath I. The Lymphoid Neoplasms 3ed. CRC Press; 2010.</ref> However, the exact B cell maturation stage involved in the development of hairy cell leukemia is still unclear.<ref name="found">What is Hairy Cell Leukemia? Hairy Cell Leukemia Foundation (2015) https://www.hairycellleukemia.org/about-hcl/what-is-hairy-cell-leukemia/ Accessed on October, 19 2015</ref> The most common gene involved in the pathogenesis of hairy cell leukemia is BRAF V600E mutations.<ref name="wiki"> Hairy cell leukemia. Wikipedia (2015) https://en.wikipedia.org/wiki/Hairy_cell_leukemia#Pathophysiology Accessed on Ocotber, 19 2015</ref> On microscopic histopathological analysis, characteristic findings of hairy cell leukemia include a small cells with "Fried egg"-like appearance, well-demarcated fuzzy borders, and a clear cytoplasm.<ref name="patho">Small cell lymphoma. Libre Pathology (2015) http://librepathology.org/wiki/index.php/Small_cell_lymphomas#Hairy_cell_leukemia Accessed on October, 8 2015</ref> | |||
==Pathogenesis== | ==Pathogenesis== | ||
* Hairy cell leukemia arises from [[B cell]]s, that are normally involved in the process of human [[immunoglobulin]]s production.<ref name="m">Magrath I. The Lymphoid Neoplasms 3ed. CRC Press; 2010.</ref> | * Hairy cell leukemia arises from [[B cell]]s, that are normally involved in the process of human [[immunoglobulin]]s production.<ref name="m">Magrath I. The Lymphoid Neoplasms 3ed. CRC Press; 2010.</ref> | ||
* However, the exact B cell maturation stage involved in the development of hairy cell leukemia is still unclear.<ref name="found">What is Hairy Cell Leukemia? Hairy Cell Leukemia Foundation (2015) https://www.hairycellleukemia.org/about-hcl/what-is-hairy-cell-leukemia/ Accessed on October, 19 2015</ref> | * However, the exact B cell maturation stage involved in the development of hairy cell leukemia is still unclear.<ref name="found">What is Hairy Cell Leukemia? Hairy Cell Leukemia Foundation (2015) https://www.hairycellleukemia.org/about-hcl/what-is-hairy-cell-leukemia/ Accessed on October, 19 2015</ref> | ||
* Hairy cell leukemia may also infiltrate the [[spleen]] and [[liver]]. | * Hairy cell leukemia may also infiltrate the [[spleen]] and [[liver]]. | ||
* Extravascular hemolysis may develop due to splenic sequestration | * Extravascular hemolysis may develop due to splenic sequestration of the circulating red blood cells. | ||
* Hairy cell leukemia | * Hairy cell leukemia does not infiltrate peripheral [[lymph node]]s. | ||
* Bone marrow failure may develop among hairy cell leukemia patients due to: | * Bone marrow failure may develop among hairy cell leukemia patients due to:<ref name="wiki"> Hairy cell leukemia. Wikipedia (2015) https://en.wikipedia.org/wiki/Hairy_cell_leukemia#Pathophysiology Accessed on Ocotber, 19 2015</ref> | ||
:* [[Malignant]] cells | :* [[Malignant]] cells infiltration of the [[bone marrow]] | ||
:* Reticulin fibrosis of the bone marrow | :* [[Reticulin]] fibrosis of the bone marrow | ||
:* Dysregulated cytokine production | :* Dysregulated cytokine production | ||
* The development of [[bone marrow]] failure interferes with the normal production of [[red blood cell]]s and [[platelet]]s among hairy cell leukemia patients. | * The development of [[bone marrow]] failure interferes with the normal production of [[red blood cell]]s and [[platelet]]s among hairy cell leukemia patients.<ref name="pmid16723990">{{cite journal| author=Tiacci E, Liso A, Piris M, Falini B| title=Evolving concepts in the pathogenesis of hairy-cell leukaemia. | journal=Nat Rev Cancer | year= 2006 | volume= 6 | issue= 6 | pages= 437-48 | pmid=16723990 | doi=10.1038/nrc1888 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16723990 }} </ref> | ||
* Production of [[cytokine]]s, such as TNF α and IL-2R, provide important stimuli for [[malignant]] [[B cell]]s proliferation in hairy cell leukemia. | * Production of [[cytokine]]s, such as TNF α and IL-2R, provide important stimuli for [[malignant]] [[B cell]]s proliferation in hairy cell leukemia. | ||
* In approximately 40% of hairy cell leukemia cases, malignant cells co-express multiple colonally related IgG, IgA, and IgM isotypes. | * Leukemic cells demonstrate prolonged survival due to up-regulation of apoptosis inhibitors such as IAP1 and IAP2 by TNF α. | ||
* In approximately 40% of hairy cell leukemia cases, malignant cells co-express multiple colonally related IgG, IgA, and IgM isotypes. | |||
==Genetics== | ==Genetics== | ||
* The most common gene involved in the pathogenesis of hairy cell leukemia is BRAF V600E mutations.<ref name="wiki"> Hairy cell leukemia. Wikipedia (2015) https://en.wikipedia.org/wiki/Hairy_cell_leukemia#Pathophysiology Accessed on Ocotber, 19 2015</ref> | * The most common gene involved in the pathogenesis of hairy cell leukemia is BRAF V600E mutations.<ref name="wiki"> Hairy cell leukemia. Wikipedia (2015) https://en.wikipedia.org/wiki/Hairy_cell_leukemia#Pathophysiology Accessed on Ocotber, 19 2015</ref> | ||
* The BRAF V600E mutations is '''present''' | * The BRAF V600E mutations is '''present''' among most of the patients with hairy cell leukemia '''(classic)'''. | ||
* The BRAF V600E mutations is ''' | * The BRAF V600E mutations is '''absent''' among patients with hairy cell leukemia '''(variant)'''. | ||
* | * Molecular pathways involved in the pathogensis of hairy cell leukemia include:<ref name="pmid16723990">{{cite journal| author=Tiacci E, Liso A, Piris M, Falini B| title=Evolving concepts in the pathogenesis of hairy-cell leukaemia. | journal=Nat Rev Cancer | year= 2006 | volume= 6 | issue= 6 | pages= 437-48 | pmid=16723990 | doi=10.1038/nrc1888 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16723990 }} </ref> | ||
:* | :* p38-MAPK-JNK molecular cascade is inhibited thus suppressing the apoptotic signaling pathways. | ||
:* | :* MEK-ERK molecular cascade is activated thus amplifying the cytoprotective survival pathways. | ||
:* Phosphatidylinositol 3 kinase (PI3K)-AKT cascade is activated thus suppressing the apoptotic signaling pathways. | |||
==Associated Conditions== | ==Associated Conditions== | ||
= | * Hairy cell leukemia has been found to be associated with Trisomy 5 in a number of cases.<ref name="wiki"> Hairy cell leukemia. Wikipedia (2015) https://en.wikipedia.org/wiki/Hairy_cell_leukemia#Pathophysiology Accessed on Ocotber, 19 2015</ref> | ||
==Microscopic Pathology== | ==Microscopic Pathology== | ||
* On microscopic histopathological analysis, characteristic findings of hairy cell leukemia include:<ref name="patho">Small cell lymphoma. Libre Pathology (2015) http://librepathology.org/wiki/index.php/Small_cell_lymphomas#Hairy_cell_leukemia Accessed on October, 8 2015</ref> | |||
:* Small cells with "Fried egg"-like appearance | |||
:* Well-demarcated fuzzy cell borders | |||
:* Clear cytoplasm | |||
:* Central round nucleus | |||
:* Peri-nuclear clearing ("water-clear rim" appearance) | |||
* Illustrated below is a series of microscopic images observed in hairy cell leukemia: | |||
<gallery> | |||
Image: | |||
Hairy cell leukemia blood film.jpg|Hairy cell leukemia illustrated on a blood film<ref name="patho">Small cell lymphoma. Libre Pathology (2015) http://librepathology.org/wiki/index.php/Small_cell_lymphomas#Hairy_cell_leukemia Accessed on October, 8 2015</ref> | |||
Image: | |||
Hairy cell leukemia - high mag.jpg|Hairy cell leukemia illustrated on high magnification<ref name="patho">Small cell lymphoma. Libre Pathology (2015) http://librepathology.org/wiki/index.php/Small_cell_lymphomas#Hairy_cell_leukemia Accessed on October, 8 2015</ref> | |||
Image: | |||
800px-Hairy cell leukemia - very high mag.jpg| Hairy cell leukemia illustrated on very high magnification<ref name="patho">Small cell lymphoma. Libre Pathology (2015) http://librepathology.org/wiki/index.php/Small_cell_lymphomas#Hairy_cell_leukemia Accessed on October, 8 2015</ref> | |||
</gallery> | |||
Latest revision as of 20:22, 20 October 2015
Overview
Hairy cell leukemia arises from B cells, that are normally involved in the process of human immunoglobulins production.[1] However, the exact B cell maturation stage involved in the development of hairy cell leukemia is still unclear.[2] The most common gene involved in the pathogenesis of hairy cell leukemia is BRAF V600E mutations.[3] On microscopic histopathological analysis, characteristic findings of hairy cell leukemia include a small cells with "Fried egg"-like appearance, well-demarcated fuzzy borders, and a clear cytoplasm.[4]
Pathogenesis
- Hairy cell leukemia arises from B cells, that are normally involved in the process of human immunoglobulins production.[1]
- However, the exact B cell maturation stage involved in the development of hairy cell leukemia is still unclear.[2]
- Hairy cell leukemia may also infiltrate the spleen and liver.
- Extravascular hemolysis may develop due to splenic sequestration of the circulating red blood cells.
- Hairy cell leukemia does not infiltrate peripheral lymph nodes.
- Bone marrow failure may develop among hairy cell leukemia patients due to:[3]
- Malignant cells infiltration of the bone marrow
- Reticulin fibrosis of the bone marrow
- Dysregulated cytokine production
- The development of bone marrow failure interferes with the normal production of red blood cells and platelets among hairy cell leukemia patients.[5]
- Production of cytokines, such as TNF α and IL-2R, provide important stimuli for malignant B cells proliferation in hairy cell leukemia.
- Leukemic cells demonstrate prolonged survival due to up-regulation of apoptosis inhibitors such as IAP1 and IAP2 by TNF α.
- In approximately 40% of hairy cell leukemia cases, malignant cells co-express multiple colonally related IgG, IgA, and IgM isotypes.
Genetics
- The most common gene involved in the pathogenesis of hairy cell leukemia is BRAF V600E mutations.[3]
- The BRAF V600E mutations is present among most of the patients with hairy cell leukemia (classic).
- The BRAF V600E mutations is absent among patients with hairy cell leukemia (variant).
- Molecular pathways involved in the pathogensis of hairy cell leukemia include:[5]
- p38-MAPK-JNK molecular cascade is inhibited thus suppressing the apoptotic signaling pathways.
- MEK-ERK molecular cascade is activated thus amplifying the cytoprotective survival pathways.
- Phosphatidylinositol 3 kinase (PI3K)-AKT cascade is activated thus suppressing the apoptotic signaling pathways.
Associated Conditions
- Hairy cell leukemia has been found to be associated with Trisomy 5 in a number of cases.[3]
Microscopic Pathology
- On microscopic histopathological analysis, characteristic findings of hairy cell leukemia include:[4]
- Small cells with "Fried egg"-like appearance
- Well-demarcated fuzzy cell borders
- Clear cytoplasm
- Central round nucleus
- Peri-nuclear clearing ("water-clear rim" appearance)
- Illustrated below is a series of microscopic images observed in hairy cell leukemia:
-
![Hairy cell leukemia illustrated on a blood film[4]](/images/b/bd/Hairy_cell_leukemia_blood_film.jpg)
Hairy cell leukemia illustrated on a blood film[4]
-
![Hairy cell leukemia illustrated on high magnification[4]](/images/8/8a/Hairy_cell_leukemia_-_high_mag.jpg)
Hairy cell leukemia illustrated on high magnification[4]
-
![Hairy cell leukemia illustrated on very high magnification[4]](/images/d/dd/800px-Hairy_cell_leukemia_-_very_high_mag.jpg)
Hairy cell leukemia illustrated on very high magnification[4]
![Hairy cell leukemia illustrated on a blood film[4]](/index.php/File:Hairy_cell_leukemia_blood_film.jpg)
![Hairy cell leukemia illustrated on high magnification[4]](/index.php/File:Hairy_cell_leukemia_-_high_mag.jpg)
![Hairy cell leukemia illustrated on very high magnification[4]](/index.php/File:800px-Hairy_cell_leukemia_-_very_high_mag.jpg)
- ↑ 1.0 1.1 Magrath I. The Lymphoid Neoplasms 3ed. CRC Press; 2010.
- ↑ 2.0 2.1 What is Hairy Cell Leukemia? Hairy Cell Leukemia Foundation (2015) https://www.hairycellleukemia.org/about-hcl/what-is-hairy-cell-leukemia/ Accessed on October, 19 2015
- ↑ 3.0 3.1 3.2 3.3 Hairy cell leukemia. Wikipedia (2015) https://en.wikipedia.org/wiki/Hairy_cell_leukemia#Pathophysiology Accessed on Ocotber, 19 2015
- ↑ 4.0 4.1 4.2 4.3 4.4 Small cell lymphoma. Libre Pathology (2015) http://librepathology.org/wiki/index.php/Small_cell_lymphomas#Hairy_cell_leukemia Accessed on October, 8 2015
- ↑ 5.0 5.1 Tiacci E, Liso A, Piris M, Falini B (2006). "Evolving concepts in the pathogenesis of hairy-cell leukaemia". Nat Rev Cancer. 6 (6): 437–48. doi:10.1038/nrc1888. PMID 16723990.