Hairy cell leukemia pathophysiology: Difference between revisions
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__NOTOC__ | __NOTOC__ | ||
{{Hairy cell leukemia}} | {{Hairy cell leukemia}} | ||
{{CMG}}; {{AE}} {{VKG}} {{HL}} | {{CMG}}; {{AE}} {{VKG}}, {{HL}}; {{GRR}} {{Nat}} | ||
==Overview== | ==Overview== | ||
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==Pathogenesis== | ==Pathogenesis== | ||
* [[Hairy cell leukemia]] arises from [[B cell]]s, | * [[Hairy cell leukemia]] arises from [[B cell]]s, which are normally involved in the process of human [[immunoglobulin]]s production.<ref name="pmid167239902">{{cite journal |vauthors=Tiacci E, Liso A, Piris M, Falini B |title=Evolving concepts in the pathogenesis of hairy-cell leukaemia |journal=Nat. Rev. Cancer |volume=6 |issue=6 |pages=437–48 |date=June 2006 |pmid=16723990 |doi=10.1038/nrc1888 |url=}}</ref> | ||
* The exact [[B cell]] [[maturation]] stage involved in the development of [[hairy cell leukemia]] is still unclear.<ref name="pmid16990106">{{cite journal |vauthors=Matutes E |title=Immunophenotyping and differential diagnosis of hairy cell leukemia |journal=Hematol. Oncol. Clin. North Am. |volume=20 |issue=5 |pages=1051–63 |date=October 2006 |pmid=16990106 |doi=10.1016/j.hoc.2006.06.012 |url=}}</ref> | * The exact [[B cell]] [[maturation]] stage involved in the development of [[hairy cell leukemia]] is still unclear.<ref name="pmid16990106">{{cite journal |vauthors=Matutes E |title=Immunophenotyping and differential diagnosis of hairy cell leukemia |journal=Hematol. Oncol. Clin. North Am. |volume=20 |issue=5 |pages=1051–63 |date=October 2006 |pmid=16990106 |doi=10.1016/j.hoc.2006.06.012 |url=}}</ref> | ||
* [[Bone marrow failure]] may develop among [[hairy cell leukemia]] patients due to: | * [[Bone marrow failure]] may develop among [[hairy cell leukemia]] patients due to: | ||
| Line 16: | Line 16: | ||
* [[Leukemic]] cells may also infiltrate both the [[spleen]] and [[liver]] and leads to [[organomegaly]]. | * [[Leukemic]] cells may also infiltrate both the [[spleen]] and [[liver]] and leads to [[organomegaly]]. | ||
* Extravascular [[hemolysis]] may develop due to splenic sequestration of the circulating [[red blood cell]]s. | * Extravascular [[hemolysis]] may develop due to splenic sequestration of the circulating [[red blood cell]]s. | ||
* In very rare occasions [[leukemic]] cells may infiltrate the peripheral [[lymph node]]s. | * In very rare occasions, [[leukemic]] cells may infiltrate the peripheral [[lymph node]]s. | ||
* Production of [[cytokine]]s, such as [[TNF alpha]] and [[IL-2]], provide important stimuli for [[malignant]] [[B cell]]s proliferation in [[hairy cell leukemia]]. | * Production of [[cytokine]]s, such as [[TNF alpha]] and [[IL-2]], provide important stimuli for [[malignant]] [[B cell]]s proliferation in [[hairy cell leukemia]]. | ||
* [[Leukemic]] cells demonstrate prolonged survival due to the up-regulation of [[apoptosis]]-inhibitors such as ''IAP1'' and ''IAP2'' by [[TNF alpha]]. | * [[Leukemic]] cells demonstrate prolonged survival due to the up-regulation of [[apoptosis]]-inhibitors such as ''IAP1'' and ''IAP2'' by [[TNF alpha]]. | ||
* In approximately 40% of [[hairy cell leukemia]] cases, malignant cells co-express multiple clonally related [[IgG]], [[IgA]], and [[IgM]] isotypes. | * In approximately 40% of [[hairy cell leukemia]] cases, malignant cells co-express multiple clonally-related [[IgG]], [[IgA]], and [[IgM]] isotypes. | ||
==Genetics== | ==Genetics== | ||
* The most common gene involved in the [[pathogenesis]] of [[hairy cell leukemia]] is [[BRAF]] V600E mutation.<ref name="pmid16880237">{{cite journal |vauthors=Wanko SO, de Castro C |title=Hairy cell leukemia: an elusive but treatable disease |journal=Oncologist |volume=11 |issue=7 |pages=780–9 |date=2006 |pmid=16880237 |doi=10.1634/theoncologist.11-7-780 |url=}}</ref><ref name="pmid18704161">{{cite journal |vauthors=Ng PC, Levy S, Huang J, Stockwell TB, Walenz BP, Li K, Axelrod N, Busam DA, Strausberg RL, Venter JC |title=Genetic variation in an individual human exome |journal=PLoS Genet. |volume=4 |issue=8 |pages=e1000160 |date=August 2008 |pmid=18704161 |pmc=2493042 |doi=10.1371/journal.pgen.1000160 |url=}}</ref><ref name="pmid233479032">{{cite journal |vauthors=Shao H, Calvo KR, Grönborg M, Tembhare PR, Kreitman RJ, Stetler-Stevenson M, Yuan CM |title=Distinguishing hairy cell leukemia variant from hairy cell leukemia: development and validation of diagnostic criteria |journal=Leuk. Res. |volume=37 |issue=4 |pages=401–409 |date=April 2013 |pmid=23347903 |pmc=5575750 |doi=10.1016/j.leukres.2012.11.021 |url=}}</ref><ref name="pmid22028477">{{cite journal |vauthors=Tiacci E, Schiavoni G, Forconi F, Santi A, Trentin L, Ambrosetti A, Cecchini D, Sozzi E, Francia di Celle P, Di Bello C, Pulsoni A, Foà R, Inghirami G, Falini B |title=Simple genetic diagnosis of hairy cell leukemia by sensitive detection of the BRAF-V600E mutation |journal=Blood |volume=119 |issue=1 |pages=192–5 |date=January 2012 |pmid=22028477 |doi=10.1182/blood-2011-08-371179 |url=}}</ref><ref name="pmid22331186">{{cite journal |vauthors=Schnittger S, Bacher U, Haferlach T, Wendland N, Ulke M, Dicker F, Grossmann V, Haferlach C, Kern W |title=Development and validation of a real-time quantification assay to detect and monitor BRAFV600E mutations in hairy cell leukemia |journal=Blood |volume=119 |issue=13 |pages=3151–4 |date=March 2012 |pmid=22331186 |doi=10.1182/blood-2011-10-383323 |url=}}</ref> | * The most common gene involved in the [[pathogenesis]] of [[hairy cell leukemia]] is [[BRAF]] V600E mutation.<ref name="pmid16880237">{{cite journal |vauthors=Wanko SO, de Castro C |title=Hairy cell leukemia: an elusive but treatable disease |journal=Oncologist |volume=11 |issue=7 |pages=780–9 |date=2006 |pmid=16880237 |doi=10.1634/theoncologist.11-7-780 |url=}}</ref><ref name="pmid18704161">{{cite journal |vauthors=Ng PC, Levy S, Huang J, Stockwell TB, Walenz BP, Li K, Axelrod N, Busam DA, Strausberg RL, Venter JC |title=Genetic variation in an individual human exome |journal=PLoS Genet. |volume=4 |issue=8 |pages=e1000160 |date=August 2008 |pmid=18704161 |pmc=2493042 |doi=10.1371/journal.pgen.1000160 |url=}}</ref><ref name="pmid233479032">{{cite journal |vauthors=Shao H, Calvo KR, Grönborg M, Tembhare PR, Kreitman RJ, Stetler-Stevenson M, Yuan CM |title=Distinguishing hairy cell leukemia variant from hairy cell leukemia: development and validation of diagnostic criteria |journal=Leuk. Res. |volume=37 |issue=4 |pages=401–409 |date=April 2013 |pmid=23347903 |pmc=5575750 |doi=10.1016/j.leukres.2012.11.021 |url=}}</ref><ref name="pmid22028477">{{cite journal |vauthors=Tiacci E, Schiavoni G, Forconi F, Santi A, Trentin L, Ambrosetti A, Cecchini D, Sozzi E, Francia di Celle P, Di Bello C, Pulsoni A, Foà R, Inghirami G, Falini B |title=Simple genetic diagnosis of hairy cell leukemia by sensitive detection of the BRAF-V600E mutation |journal=Blood |volume=119 |issue=1 |pages=192–5 |date=January 2012 |pmid=22028477 |doi=10.1182/blood-2011-08-371179 |url=}}</ref><ref name="pmid22331186">{{cite journal |vauthors=Schnittger S, Bacher U, Haferlach T, Wendland N, Ulke M, Dicker F, Grossmann V, Haferlach C, Kern W |title=Development and validation of a real-time quantification assay to detect and monitor BRAFV600E mutations in hairy cell leukemia |journal=Blood |volume=119 |issue=13 |pages=3151–4 |date=March 2012 |pmid=22331186 |doi=10.1182/blood-2011-10-383323 |url=}}</ref> | ||
* The [[BRAF]] V600E | * The [[BRAF]] V600E mutation is '''present''' among most of the patients with [[hairy cell leukemia]] '''(classic)'''.<ref name="pmid22210875">{{cite journal |vauthors=Xi L, Arons E, Navarro W, Calvo KR, Stetler-Stevenson M, Raffeld M, Kreitman RJ |title=Both variant and IGHV4-34-expressing hairy cell leukemia lack the BRAF V600E mutation |journal=Blood |volume=119 |issue=14 |pages=3330–2 |date=April 2012 |pmid=22210875 |pmc=3321859 |doi=10.1182/blood-2011-09-379339 |url=}}</ref> | ||
* The BRAF V600E | * The BRAF V600E mutation is '''absent''' among patients with hairy cell leukemia '''(variant)'''.<ref name="pmid21910720">{{cite journal |vauthors=Boyd EM, Bench AJ, van 't Veer MB, Wright P, Bloxham DM, Follows GA, Scott MA |title=High resolution melting analysis for detection of BRAF exon 15 mutations in hairy cell leukaemia and other lymphoid malignancies |journal=Br. J. Haematol. |volume=155 |issue=5 |pages=609–12 |date=December 2011 |pmid=21910720 |doi=10.1111/j.1365-2141.2011.08868.x |url=}}</ref> | ||
* [[Molecular]] pathways involved in the [[pathogenesis]] 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> | * [[Molecular]] pathways involved in the [[pathogenesis]] 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> | ||
:* The ''p38-[[MAPK]]-[[JNK]]'' cascade is inhibited which will suppress the [[apoptotic]] signaling pathways. | :* The ''p38-[[MAPK]]-[[JNK]]'' cascade is inhibited, which will suppress the [[apoptotic]] signaling pathways. | ||
:* The ''MEK-[[ERK]]'' cascade is activated which will amplify the cytoprotective survival pathways.<ref name="pmid21663470">{{cite journal |vauthors=Tiacci E, Trifonov V, Schiavoni G, Holmes A, Kern W, Martelli MP, Pucciarini A, Bigerna B, Pacini R, Wells VA, Sportoletti P, Pettirossi V, Mannucci R, Elliott O, Liso A, Ambrosetti A, Pulsoni A, Forconi F, Trentin L, Semenzato G, Inghirami G, Capponi M, Di Raimondo F, Patti C, Arcaini L, Musto P, Pileri S, Haferlach C, Schnittger S, Pizzolo G, Foà R, Farinelli L, Haferlach T, Pasqualucci L, Rabadan R, Falini B |title=BRAF mutations in hairy-cell leukemia |journal=N. Engl. J. Med. |volume=364 |issue=24 |pages=2305–15 |date=June 2011 |pmid=21663470 |pmc=3689585 |doi=10.1056/NEJMoa1014209 |url=}}</ref> | :* The ''MEK-[[ERK]]'' cascade is activated which will amplify the cytoprotective survival pathways.<ref name="pmid21663470">{{cite journal |vauthors=Tiacci E, Trifonov V, Schiavoni G, Holmes A, Kern W, Martelli MP, Pucciarini A, Bigerna B, Pacini R, Wells VA, Sportoletti P, Pettirossi V, Mannucci R, Elliott O, Liso A, Ambrosetti A, Pulsoni A, Forconi F, Trentin L, Semenzato G, Inghirami G, Capponi M, Di Raimondo F, Patti C, Arcaini L, Musto P, Pileri S, Haferlach C, Schnittger S, Pizzolo G, Foà R, Farinelli L, Haferlach T, Pasqualucci L, Rabadan R, Falini B |title=BRAF mutations in hairy-cell leukemia |journal=N. Engl. J. Med. |volume=364 |issue=24 |pages=2305–15 |date=June 2011 |pmid=21663470 |pmc=3689585 |doi=10.1056/NEJMoa1014209 |url=}}</ref> | ||
:* The [[Phosphatidylinositol 3-phosphate|phosphatidylinositol 3 kinase]] ''([[Phosphoinositide 3-kinase|PI3K]])-[[AKT]]'' [[cascade]] is activated thus suppressing the [[apoptotic]] signaling pathways. | :* The [[Phosphatidylinositol 3-phosphate|phosphatidylinositol 3 kinase]] ''([[Phosphoinositide 3-kinase|PI3K]])-[[AKT]]'' [[cascade]] is activated thus suppressing the [[apoptotic]] signaling pathways. | ||
Latest revision as of 17:20, 8 April 2019
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vamsikrishna Gunnam M.B.B.S [2], Haytham Allaham, M.D. [3]; Grammar Reviewer: Natalie Harpenau, B.S.[4]
Overview
Hairy cell leukemia arises from B cells that are normally involved in the process of human immunoglobulins production. However, the exact B cell maturation stage involved in the development of hairy cell leukemia is still unclear. The most common gene involved in the pathogenesis of hairy cell leukemia is BRAF V600E mutation. On microscopic histopathological analysis, characteristic findings of hairy cell leukemia include small cells with "fried egg" like appearance, well-demarcated thread-like cytoplasmic extensions, and a clear cytoplasm.
Pathogenesis
- Hairy cell leukemia arises from B cells, which are normally involved in the process of human immunoglobulins production.[1]
- The exact B cell maturation stage involved in the development of hairy cell leukemia is still unclear.[2]
- Bone marrow failure may develop among hairy cell leukemia patients due to:
- Malignant cells infiltration of the bone marrow, resulting in bone marrow failure or pancytopenia
- 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.
- Leukemic cells may also infiltrate both the spleen and liver and leads to organomegaly.
- Extravascular hemolysis may develop due to splenic sequestration of the circulating red blood cells.
- In very rare occasions, leukemic cells may infiltrate the peripheral lymph nodes.
- Production of cytokines, such as TNF alpha and IL-2, provide important stimuli for malignant B cells proliferation in hairy cell leukemia.
- Leukemic cells demonstrate prolonged survival due to the up-regulation of apoptosis-inhibitors such as IAP1 and IAP2 by TNF alpha.
- In approximately 40% of hairy cell leukemia cases, malignant cells co-express multiple clonally-related IgG, IgA, and IgM isotypes.
Genetics
- The most common gene involved in the pathogenesis of hairy cell leukemia is BRAF V600E mutation.[3][4][5][6][7]
- The BRAF V600E mutation is present among most of the patients with hairy cell leukemia (classic).[8]
- The BRAF V600E mutation is absent among patients with hairy cell leukemia (variant).[9]
- Molecular pathways involved in the pathogenesis of hairy cell leukemia include:[10]
- The p38-MAPK-JNK cascade is inhibited, which will suppress the apoptotic signaling pathways.
- The MEK-ERK cascade is activated which will amplify the cytoprotective survival pathways.[11]
- The 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 reported cases.
Microscopic Pathology
- On microscopic histopathological analysis, characteristic findings of hairy cell leukemia include:
- Small cells with "fried egg" like appearance
- Well-demarcated thread-like cytoplasmic extensions
- Clear cytoplasm
- Central round nucleus
- Perinuclear clearing ("water-clear rim" appearance)
- A positive tartrate-resistant acid phosphatase (TRAP) stain is a key diagnostic feature for hairy cell leukemia.[12]
- On immunohistochemistry, characteristic findings of hairy cell leukemia include:[13][14]
- Annexin A1 +ve
- CD20 +ve
- CD25 +ve
- CD103 +ve
- Illustrated below is a series of microscopic images observed in hairy cell leukemia:
-
![Hairy cell leukemia illustrated on a blood film[16]](/images/b/bd/Hairy_cell_leukemia_blood_film.jpg)
Hairy cell leukemia illustrated on a blood film[16]
-
![Hairy cell leukemia illustrated on high magnification[16]](/images/8/8a/Hairy_cell_leukemia_-_high_mag.jpg)
Hairy cell leukemia illustrated on high magnification[16]
-
![Hairy cell leukemia illustrated on very high magnification[16]](/images/d/dd/800px-Hairy_cell_leukemia_-_very_high_mag.jpg)
Hairy cell leukemia illustrated on very high magnification[16]
![Hairy cell leukemia illustrated on a blood film[16]](/index.php/File:Hairy_cell_leukemia_blood_film.jpg)
![Hairy cell leukemia illustrated on high magnification[16]](/index.php/File:Hairy_cell_leukemia_-_high_mag.jpg)
![Hairy cell leukemia illustrated on very high magnification[16]](/index.php/File:800px-Hairy_cell_leukemia_-_very_high_mag.jpg)
References
- ↑ Tiacci E, Liso A, Piris M, Falini B (June 2006). "Evolving concepts in the pathogenesis of hairy-cell leukaemia". Nat. Rev. Cancer. 6 (6): 437–48. doi:10.1038/nrc1888. PMID 16723990.
- ↑ Matutes E (October 2006). "Immunophenotyping and differential diagnosis of hairy cell leukemia". Hematol. Oncol. Clin. North Am. 20 (5): 1051–63. doi:10.1016/j.hoc.2006.06.012. PMID 16990106.
- ↑ Wanko SO, de Castro C (2006). "Hairy cell leukemia: an elusive but treatable disease". Oncologist. 11 (7): 780–9. doi:10.1634/theoncologist.11-7-780. PMID 16880237.
- ↑ Ng PC, Levy S, Huang J, Stockwell TB, Walenz BP, Li K, Axelrod N, Busam DA, Strausberg RL, Venter JC (August 2008). "Genetic variation in an individual human exome". PLoS Genet. 4 (8): e1000160. doi:10.1371/journal.pgen.1000160. PMC 2493042. PMID 18704161.
- ↑ Shao H, Calvo KR, Grönborg M, Tembhare PR, Kreitman RJ, Stetler-Stevenson M, Yuan CM (April 2013). "Distinguishing hairy cell leukemia variant from hairy cell leukemia: development and validation of diagnostic criteria". Leuk. Res. 37 (4): 401–409. doi:10.1016/j.leukres.2012.11.021. PMC 5575750. PMID 23347903.
- ↑ Tiacci E, Schiavoni G, Forconi F, Santi A, Trentin L, Ambrosetti A, Cecchini D, Sozzi E, Francia di Celle P, Di Bello C, Pulsoni A, Foà R, Inghirami G, Falini B (January 2012). "Simple genetic diagnosis of hairy cell leukemia by sensitive detection of the BRAF-V600E mutation". Blood. 119 (1): 192–5. doi:10.1182/blood-2011-08-371179. PMID 22028477.
- ↑ Schnittger S, Bacher U, Haferlach T, Wendland N, Ulke M, Dicker F, Grossmann V, Haferlach C, Kern W (March 2012). "Development and validation of a real-time quantification assay to detect and monitor BRAFV600E mutations in hairy cell leukemia". Blood. 119 (13): 3151–4. doi:10.1182/blood-2011-10-383323. PMID 22331186.
- ↑ Xi L, Arons E, Navarro W, Calvo KR, Stetler-Stevenson M, Raffeld M, Kreitman RJ (April 2012). "Both variant and IGHV4-34-expressing hairy cell leukemia lack the BRAF V600E mutation". Blood. 119 (14): 3330–2. doi:10.1182/blood-2011-09-379339. PMC 3321859. PMID 22210875.
- ↑ Boyd EM, Bench AJ, van 't Veer MB, Wright P, Bloxham DM, Follows GA, Scott MA (December 2011). "High resolution melting analysis for detection of BRAF exon 15 mutations in hairy cell leukaemia and other lymphoid malignancies". Br. J. Haematol. 155 (5): 609–12. doi:10.1111/j.1365-2141.2011.08868.x. PMID 21910720.
- ↑ 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.
- ↑ Tiacci E, Trifonov V, Schiavoni G, Holmes A, Kern W, Martelli MP, Pucciarini A, Bigerna B, Pacini R, Wells VA, Sportoletti P, Pettirossi V, Mannucci R, Elliott O, Liso A, Ambrosetti A, Pulsoni A, Forconi F, Trentin L, Semenzato G, Inghirami G, Capponi M, Di Raimondo F, Patti C, Arcaini L, Musto P, Pileri S, Haferlach C, Schnittger S, Pizzolo G, Foà R, Farinelli L, Haferlach T, Pasqualucci L, Rabadan R, Falini B (June 2011). "BRAF mutations in hairy-cell leukemia". N. Engl. J. Med. 364 (24): 2305–15. doi:10.1056/NEJMoa1014209. PMC 3689585. PMID 21663470.
- ↑ Cawley JC (October 2006). "The pathophysiology of the hairy cell". Hematol. Oncol. Clin. North Am. 20 (5): 1011–21. doi:10.1016/j.hoc.2006.06.002. PMID 16990104.
- ↑ Matutes E, Wotherspoon A, Catovsky D (March 2003). "The variant form of hairy-cell leukaemia". Best Pract Res Clin Haematol. 16 (1): 41–56. PMID 12670464.
- ↑ Forconi F, Raspadori D, Lenoci M, Lauria F (February 2005). "Absence of surface CD27 distinguishes hairy cell leukemia from other leukemic B-cell malignancies". Haematologica. 90 (2): 266–8. PMID 15710587.
- ↑ Shao H, Calvo KR, Grönborg M, Tembhare PR, Kreitman RJ, Stetler-Stevenson M, Yuan CM (April 2013). "Distinguishing hairy cell leukemia variant from hairy cell leukemia: development and validation of diagnostic criteria". Leuk. Res. 37 (4): 401–409. doi:10.1016/j.leukres.2012.11.021. PMC 5575750. PMID 23347903.
- ↑ 16.0 16.1 16.2 Small cell lymphoma. Libre Pathology (2015) http://librepathology.org/wiki/index.php/Small_cell_lymphomas#Hairy_cell_leukemia Accessed on October, 8 2015