|
|
| Line 1: |
Line 1: |
| __NOTOC__ | | __NOTOC__ |
| {{Hairy cell leukemia}} | | {{Hairy cell leukemia}} |
| {{CMG}} {{AE}}{{HL}} | | {{CMG}} |
|
| |
|
| ==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== | | ==Pathophysiology== |
| * 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 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]]. |
| * 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]].
| |
| * Extravascular hemolysis may develop due to splenic sequestration of the circulating red blood cells.
| |
| * 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>
| |
| :* [[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 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.
| |
| * 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 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:<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==
| | 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. |
| * 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==
| |
| * 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>
| |
|
| |
|
| ==References== | | ==References== |