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* 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 does not infiltrate peripheral [[lymph node]]s. | * Hairy cell leukemia does not infiltrate peripheral [[lymph node]]s. | ||
* 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> | * 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. | ||
* 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. | ||
* | * Leukemic cells demonstrate prolonged survival due to up-regulation of apoptosis inhibitors such as IAP1 and IAP2 by TNF α.<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> | ||
* In approximately 40% of hairy cell leukemia cases, malignant cells co-express multiple colonally related IgG, IgA, and IgM isotypes.<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> | * In approximately 40% of hairy cell leukemia cases, malignant cells co-express multiple colonally related IgG, IgA, and IgM isotypes.<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> | ||
==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> | ||
Revision as of 19:51, 20 October 2015
Overview
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.
- 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.[4]
- In approximately 40% of hairy cell leukemia cases, malignant cells co-express multiple colonally related IgG, IgA, and IgM isotypes.[4]
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:[4]
- 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
Gross Pathology
Microscopic Pathology
- ↑ Magrath I. The Lymphoid Neoplasms 3ed. CRC Press; 2010.
- ↑ 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 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 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.