Hairy cell leukemia pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
 
(48 intermediate revisions by 8 users not shown)
Line 1: Line 1:
__NOTOC__
{{Hairy cell leukemia}}
{{Hairy cell leukemia}}
{{CMG}}
{{CMG}}; {{AE}} {{VKG}}, {{HL}}; {{GRR}} {{Nat}}


==Overview==
==Overview==
[[Hairy cell leukemia]] arises from  [[B cell]]s that are normally involved in the process of human [[immunoglobulin]]s 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]].


==Pathophysiology of Hairy Cell Leukemia==
==Pathogenesis==
Hairy cells are nearly mature, activated clonal cells with signs of VH gene differentiation.<ref>{{cite web |url=http://theoncologist.alphamedpress.org/cgi/content/full/11/7/780 |title=Hairy Cell Leukemia: An Elusive but Treatable Disease -- Wanko and de Castro 11 (7): 780 -- The Oncologist |accessdate=2007-09-10 |format= |work=}}</ref> They may be related to [[memory cells]].
* [[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>
* [[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 cell]]s and [[platelet]]s 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 cell]]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]].
* [[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.


While there are few [[Comparative genomic hybridization|genomic]] imbalances in the hairy cells, the [[expression]] of genes is dysregulated in a complex and specific pattern. The cells underexpress 3p24, 3p21, 3q13.3-q22, 4p16, 11q23, 14q22-q24, 15q21-q22, 15q24-q25, and 17q22-q24 and overexpress 13q31 and Xq13.3-q21.<ref>{{cite web |url=http://bloodjournal.hematologylibrary.org/cgi/content/abstract/bloodjournal;104/1/250 |title=Comparative expressed sequence hybridization studies of hairy cell leukemia show uniform expression profile and imprint of spleen signature -- Vanhentenrijk et al. 104 (1): 250 -- Blood |accessdate=2007-09-10 |format= |work=}}</ref> It has not yet been demonstrated that any of these changes have any practical significance to the patient.
==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 [[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 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>
:* 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 [[Phosphatidylinositol 3-phosphate|phosphatidylinositol 3 kinase]] ''([[Phosphoinositide 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|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 space|Perinuclear]] clearing ("water-clear rim" appearance)
* A positive [[tartrate-resistant acid phosphatase]] (TRAP) stain is a key diagnostic feature for hairy cell leukemia.<ref name="pmid16990104">{{cite journal |vauthors=Cawley JC |title=The pathophysiology of the hairy cell |journal=Hematol. Oncol. Clin. North Am. |volume=20 |issue=5 |pages=1011–21 |date=October 2006 |pmid=16990104 |doi=10.1016/j.hoc.2006.06.002 |url=}}</ref>
* On [[immunohistochemistry]], characteristic findings of hairy cell [[leukemia]] include:<ref name="pmid12670464">{{cite journal |vauthors=Matutes E, Wotherspoon A, Catovsky D |title=The variant form of hairy-cell leukaemia |journal=Best Pract Res Clin Haematol |volume=16 |issue=1 |pages=41–56 |date=March 2003 |pmid=12670464 |doi= |url=}}</ref><ref name="pmid15710587">{{cite journal |vauthors=Forconi F, Raspadori D, Lenoci M, Lauria F |title=Absence of surface CD27 distinguishes hairy cell leukemia from other leukemic B-cell malignancies |journal=Haematologica |volume=90 |issue=2 |pages=266–8 |date=February 2005 |pmid=15710587 |doi= |url=}}</ref>
:* [[Annexin A1]] +ve
:* [[CD20]] +ve
:* [[CD25]] +ve
:* [[CD103]] +ve
* On flow cytometry, characteristic findings of hairy cell [[leukemia]] include:<ref name="pmid23347903">{{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>
:* [[CD19]] +ve
:* [[CD11c]] +ve
:* [[FMC7]] +ve
* 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>


==References==
==References==
Line 14: Line 65:
[[Category:Disease]]
[[Category:Disease]]
[[Category:Types of cancer]]
[[Category:Types of cancer]]
[[Category:Hematology]]
[[Category:Hematology]]
[[Category:Oncology]]


{{WikiDoc Help Menu}}
{{WikiDoc Help Menu}}
{{WikiDoc Sources}}
{{WikiDoc Sources}}
[[Category:Up-To-Date]]
[[Category:Oncology]]
[[Category:Medicine]]
[[Category:Hematology]]
[[Category:Immunology]]

Latest revision as of 17:20, 8 April 2019

Hairy cell leukemia Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Hairy cell leukemia from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

Staging

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

CT

MRI

Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Hairy cell leukemia pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Hairy cell leukemia pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Hairy cell leukemia pathophysiology

CDC on Hairy cell leukemia pathophysiology

Hairy cell leukemia pathophysiology in the news

Blogs on Hairy cell leukemia pathophysiology

Directions to Hospitals Treating Hairy cell leukemia

Risk calculators and risk factors for Hairy cell leukemia pathophysiology

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

Genetics

Associated Conditions

Microscopic Pathology

  • On flow cytometry, characteristic findings of hairy cell leukemia include:[15]
  • Illustrated below is a series of microscopic images observed in hairy cell leukemia:
  • Hairy cell leukemia illustrated on a blood film[16]

    Hairy cell leukemia illustrated on a blood film[16]

  • Hairy cell leukemia illustrated on high magnification[16]

    Hairy cell leukemia illustrated on high magnification[16]

  • Hairy cell leukemia illustrated on very high magnification[16]

    Hairy cell leukemia illustrated on very high magnification[16]

References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ 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.
  15. ↑ 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. ↑ 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


Template:WikiDoc Sources

Retrieved from "https://www.wikidoc.org/index.php?title=Hairy_cell_leukemia_pathophysiology&oldid=1561885"