Mast cell leukemia pathophysiology: Difference between revisions
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__NOTOC__ | __NOTOC__ | ||
{{Mast cell leukemia}} | {{Mast cell leukemia}} | ||
{{CMG}};{{AE}}{{NM}} | {{CMG}};{{AE}}{{NM}}, {{S.G.}} | ||
==Overview== | ==Overview== | ||
Genes involved in the pathogenesis of mast cell leukemia include ''KIT'' D816V | [[Gene|Genes]] involved in the [[pathogenesis]] of [[mast cell]] [[leukemia]] include ''KIT'' D816V and non-''KIT'' D816V.<ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref><ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref><ref name="KristensenVestergaard2011">{{cite journal|last1=Kristensen|first1=Thomas|last2=Vestergaard|first2=Hanne|last3=Møller|first3=Michael Boe|title=Improved Detection of the KIT D816V Mutation in Patients with Systemic Mastocytosis Using a Quantitative and Highly Sensitive Real-Time qPCR Assay|journal=The Journal of Molecular Diagnostics|volume=13|issue=2|year=2011|pages=180–188|issn=15251578|doi=10.1016/j.jmoldx.2010.10.004}}</ref> There are no characteristic findings of mast cell leukemia on [[gross pathology]].<ref name="Grosspathology">Horvai AE, Link TM. Bone and Soft Tissue Pathology. Elsevier Health Sciences (2012). http://books.google.com?id=p2DV6VWdXx8C. Accessed on November 30, 2015.</ref> On [[microscopic]] [[Histopathology|histopathological]] [[analysis]], multifocal sheets and clusters of [[Mast cell|mast cells]] in [[bone marrow]] sections are findings of mast cell leukemia.<ref name="ValentSotlar2014">{{cite journal|last1=Valent|first1=P.|last2=Sotlar|first2=K.|last3=Sperr|first3=W. R.|last4=Escribano|first4=L.|last5=Yavuz|first5=S.|last6=Reiter|first6=A.|last7=George|first7=T. I.|last8=Kluin-Nelemans|first8=H. C.|last9=Hermine|first9=O.|last10=Butterfield|first10=J. H.|last11=Hagglund|first11=H.|last12=Ustun|first12=C.|last13=Hornick|first13=J. L.|last14=Triggiani|first14=M.|last15=Radia|first15=D.|last16=Akin|first16=C.|last17=Hartmann|first17=K.|last18=Gotlib|first18=J.|last19=Schwartz|first19=L. B.|last20=Verstovsek|first20=S.|last21=Orfao|first21=A.|last22=Metcalfe|first22=D. D.|last23=Arock|first23=M.|last24=Horny|first24=H.- P.|title=Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal|journal=Annals of Oncology|volume=25|issue=9|year=2014|pages=1691–1700|issn=0923-7534|doi=10.1093/annonc/mdu047}}</ref> | ||
==Pathogenesis== | ==Pathogenesis== | ||
*[[Mutation]] of ''[[CD117|KIT]]'' is a [[hallmark]] of the mast cell leukemia. | |||
*[[Adult]]-type [[human]] [[mastocytosis]] is characterized by [[Mutation|mutations]] in c-''KIT'' at [[codon]] 816, which cause constitutive activation of KIT [[kinase]]. | |||
*Mutation of | |||
*Adult-type human mastocytosis is characterized by mutations in c-''KIT'' at codon 816, which cause constitutive activation of KIT kinase. | |||
*Different classes of activating ''KIT'' mutations respond differentially to KIT inhibitors depending on the site and type of mutation. | *Different classes of activating ''KIT'' mutations respond differentially to KIT inhibitors depending on the site and type of mutation. | ||
*D816V c-''KIT'' mutation is the most frequent mutation, found in more than 80% of adult patients with systemic mastocytosis especially in the aggressive forms with a frequency of more than 95% in mast cell leukemia patients.<ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref> | *D816V c-''KIT'' mutation is the most frequent mutation, found in more than 80% of adult patients with systemic mastocytosis especially in the aggressive forms with a frequency of more than 95% in mast cell leukemia patients.<ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref> | ||
==Associated | *[[Mutation|Mutations]] in ''SRSF2'', ''ASXL1'' or ''RUNX1'' are founded in mast cell leukemia patient.<ref name="JawharSchwaab2017">{{cite journal|last1=Jawhar|first1=Mohamad|last2=Schwaab|first2=Juliana|last3=Meggendorfer|first3=Manja|last4=Naumann|first4=Nicole|last5=Horny|first5=Hans-Peter|last6=Sotlar|first6=Karl|last7=Haferlach|first7=Torsten|last8=Schmitt|first8=Karla|last9=Fabarius|first9=Alice|last10=Valent|first10=Peter|last11=Hofmann|first11=Wolf-Karsten|last12=Cross|first12=Nicholas C.P.|last13=Metzgeroth|first13=Georgia|last14=Reiter|first14=Andreas|title=The clinical and molecular diversity of mast cell leukemia with or without associated hematologic neoplasm|journal=Haematologica|volume=102|issue=6|year=2017|pages=1035–1043|issn=0390-6078|doi=10.3324/haematol.2017.163964}}</ref> | ||
*The majority patients with mast cell leukemai have signs of organ damage.<ref name="JawharSchwaab2017">{{cite journal|last1=Jawhar|first1=Mohamad|last2=Schwaab|first2=Juliana|last3=Meggendorfer|first3=Manja|last4=Naumann|first4=Nicole|last5=Horny|first5=Hans-Peter|last6=Sotlar|first6=Karl|last7=Haferlach|first7=Torsten|last8=Schmitt|first8=Karla|last9=Fabarius|first9=Alice|last10=Valent|first10=Peter|last11=Hofmann|first11=Wolf-Karsten|last12=Cross|first12=Nicholas C.P.|last13=Metzgeroth|first13=Georgia|last14=Reiter|first14=Andreas|title=The clinical and molecular diversity of mast cell leukemia with or without associated hematologic neoplasm|journal=Haematologica|volume=102|issue=6|year=2017|pages=1035–1043|issn=0390-6078|doi=10.3324/haematol.2017.163964}}</ref> | |||
==Genetics== | |||
[[Gene|Genes]] involved in the [[pathogenesis]] of mast cell leukemia include:<ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref><ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref><ref name="KristensenVestergaard2011">{{cite journal|last1=Kristensen|first1=Thomas|last2=Vestergaard|first2=Hanne|last3=Møller|first3=Michael Boe|title=Improved Detection of the KIT D816V Mutation in Patients with Systemic Mastocytosis Using a Quantitative and Highly Sensitive Real-Time qPCR Assay|journal=The Journal of Molecular Diagnostics|volume=13|issue=2|year=2011|pages=180–188|issn=15251578|doi=10.1016/j.jmoldx.2010.10.004}}</ref> | |||
*''KIT'' D816V | |||
*non-''KIT'' D816V | |||
==Associated conditions== | |||
Mast cell leukemia may be associated with [[systemic mastocytosis]].<ref name="Georgin-LavialleLhermitte2012">{{cite journal|last1=Georgin-Lavialle|first1=S.|last2=Lhermitte|first2=L.|last3=Dubreuil|first3=P.|last4=Chandesris|first4=M.-O.|last5=Hermine|first5=O.|last6=Damaj|first6=G.|title=Mast cell leukemia|journal=Blood|volume=121|issue=8|year=2012|pages=1285–1295|issn=0006-4971|doi=10.1182/blood-2012-07-442400}}</ref> | |||
==Gross Pathology== | ==Gross Pathology== | ||
There are no characteristic findings of mast cell leukemia on [[gross pathology]]. [[Gross]] specimens are not seen typically.<ref name="Grosspathology">Horvai AE, Link TM. Bone and Soft Tissue Pathology. Elsevier Health Sciences (2012). http://books.google.com?id=p2DV6VWdXx8C. Accessed on November 30, 2015.</ref> | |||
==Microscopic Pathology== | ==Microscopic Pathology== | ||
On microscopic histopathological analysis, findings of mast cell leukemia include:<ref name="ValentSotlar2014">{{cite journal|last1=Valent|first1=P.|last2=Sotlar|first2=K.|last3=Sperr|first3=W. R.|last4=Escribano|first4=L.|last5=Yavuz|first5=S.|last6=Reiter|first6=A.|last7=George|first7=T. I.|last8=Kluin-Nelemans|first8=H. C.|last9=Hermine|first9=O.|last10=Butterfield|first10=J. H.|last11=Hagglund|first11=H.|last12=Ustun|first12=C.|last13=Hornick|first13=J. L.|last14=Triggiani|first14=M.|last15=Radia|first15=D.|last16=Akin|first16=C.|last17=Hartmann|first17=K.|last18=Gotlib|first18=J.|last19=Schwartz|first19=L. B.|last20=Verstovsek|first20=S.|last21=Orfao|first21=A.|last22=Metcalfe|first22=D. D.|last23=Arock|first23=M.|last24=Horny|first24=H.- P.|title=Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal|journal=Annals of Oncology|volume=25|issue=9|year=2014|pages=1691–1700|issn=0923-7534|doi=10.1093/annonc/mdu047}}</ref> | On [[microscopic]] [[histopathological]] [[analysis]], findings of mast cell leukemia include:<ref name="ValentSotlar2014">{{cite journal|last1=Valent|first1=P.|last2=Sotlar|first2=K.|last3=Sperr|first3=W. R.|last4=Escribano|first4=L.|last5=Yavuz|first5=S.|last6=Reiter|first6=A.|last7=George|first7=T. I.|last8=Kluin-Nelemans|first8=H. C.|last9=Hermine|first9=O.|last10=Butterfield|first10=J. H.|last11=Hagglund|first11=H.|last12=Ustun|first12=C.|last13=Hornick|first13=J. L.|last14=Triggiani|first14=M.|last15=Radia|first15=D.|last16=Akin|first16=C.|last17=Hartmann|first17=K.|last18=Gotlib|first18=J.|last19=Schwartz|first19=L. B.|last20=Verstovsek|first20=S.|last21=Orfao|first21=A.|last22=Metcalfe|first22=D. D.|last23=Arock|first23=M.|last24=Horny|first24=H.- P.|title=Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal|journal=Annals of Oncology|volume=25|issue=9|year=2014|pages=1691–1700|issn=0923-7534|doi=10.1093/annonc/mdu047}}</ref> | ||
*Multifocal sheets of mast cells | *Multifocal sheets of mast cells | ||
*Clusters of mast cells | *Clusters of mast cells | ||
===Gallery=== | |||
<gallery> | |||
Image: | |||
Mast_cell_leukemia_peripheral_blood_smear.jpg|<sub>Peripheral blood showing mast cell leukemia.<ref name=wikipedia>Image of peripheral blood smear of acute mast cell leukemia. Wikipedia (2015). https://en.wikipedia.org/wiki/Mast_cell_leukemia. Accessed on December 2, 2015</ref></sub></gallery> | |||
==Immunohistochemistry== | ==Immunohistochemistry== | ||
*Atypical mast cells express multiple surface antigens such as:<ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref> | *Atypical mast cells express multiple surface antigens such as:<ref name="JorisGeorgin-Lavialle2012">{{cite journal|last1=Joris|first1=Magalie|last2=Georgin-Lavialle|first2=Sophie|last3=Chandesris|first3=Marie-Olivia|last4=Lhermitte|first4=Ludovic|last5=Claisse|first5=Jean-François|last6=Canioni|first6=Danielle|last7=Hanssens|first7=Katia|last8=Damaj|first8=Gandhi|last9=Hermine|first9=Olivier|last10=Hamidou|first10=Mohammed|title=Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive|journal=Case Reports in Hematology|volume=2012|year=2012|pages=1–6|issn=2090-6560|doi=10.1155/2012/517546}}</ref> | ||
:*CD117 | :*[[CD117]] | ||
:*CD11c | :*[[CD11c]] | ||
:*CD13 | :*[[CD13]] | ||
:*CD29 | :*[[CD29]] | ||
:*CD33 | :*[[CD33]] | ||
:*CD44 | :*[[CD44]] | ||
:*CD45 | :*[[CD45]] | ||
:*CD63 | :*[[CD63]] | ||
:*CD68 | :*[[CD68]] | ||
:*CD71 | :*[[CD71]] | ||
:*CD2 | :*[[CD2]] | ||
:*CD22 | :*[[CD22]] | ||
:*CD25 | :*[[CD25]] | ||
:*CD54 | :*[[CD54]] | ||
*The role of these antigens is however not yet understood. | *The role of these antigens is however not yet understood. | ||
*CD2 and CD25 antigens are important markers | *[[CD2]] and [[CD25]] [[Antigen|antigens]] are important [[Marker|markers]]. | ||
:*Their positivity on the surface of [[Mast cell|mast cells]] constitute minor [[criteria]] for the [[diagnosis]] of mast cell disease. | |||
==References== | ==References== | ||
{{reflist|2}} | {{reflist|2}} | ||
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Latest revision as of 14:33, 23 October 2018
Mast cell leukemia Microchapters |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Nawal Muazam M.D.[2], Sogand Goudarzi, MD [3]
Overview
Genes involved in the pathogenesis of mast cell leukemia include KIT D816V and non-KIT D816V.[1][2][3] There are no characteristic findings of mast cell leukemia on gross pathology.[4] On microscopic histopathological analysis, multifocal sheets and clusters of mast cells in bone marrow sections are findings of mast cell leukemia.[5]
Pathogenesis
- Mutation of KIT is a hallmark of the mast cell leukemia.
- Adult-type human mastocytosis is characterized by mutations in c-KIT at codon 816, which cause constitutive activation of KIT kinase.
- Different classes of activating KIT mutations respond differentially to KIT inhibitors depending on the site and type of mutation.
- D816V c-KIT mutation is the most frequent mutation, found in more than 80% of adult patients with systemic mastocytosis especially in the aggressive forms with a frequency of more than 95% in mast cell leukemia patients.[1]
- Mutations in SRSF2, ASXL1 or RUNX1 are founded in mast cell leukemia patient.[6]
- The majority patients with mast cell leukemai have signs of organ damage.[6]
Genetics
Genes involved in the pathogenesis of mast cell leukemia include:[1][2][3]
- KIT D816V
- non-KIT D816V
Associated conditions
Mast cell leukemia may be associated with systemic mastocytosis.[2]
Gross Pathology
There are no characteristic findings of mast cell leukemia on gross pathology. Gross specimens are not seen typically.[4]
Microscopic Pathology
On microscopic histopathological analysis, findings of mast cell leukemia include:[5]
- Multifocal sheets of mast cells
- Clusters of mast cells
Gallery
-
Peripheral blood showing mast cell leukemia.[7]
Immunohistochemistry
- Atypical mast cells express multiple surface antigens such as:[1]
- The role of these antigens is however not yet understood.
- CD2 and CD25 antigens are important markers.
- Their positivity on the surface of mast cells constitute minor criteria for the diagnosis of mast cell disease.
References
- ↑ 1.0 1.1 1.2 1.3 Joris, Magalie; Georgin-Lavialle, Sophie; Chandesris, Marie-Olivia; Lhermitte, Ludovic; Claisse, Jean-François; Canioni, Danielle; Hanssens, Katia; Damaj, Gandhi; Hermine, Olivier; Hamidou, Mohammed (2012). "Mast Cell Leukaemia: c-KIT Mutations Are Not Always Positive". Case Reports in Hematology. 2012: 1–6. doi:10.1155/2012/517546. ISSN 2090-6560.
- ↑ 2.0 2.1 2.2 Georgin-Lavialle, S.; Lhermitte, L.; Dubreuil, P.; Chandesris, M.-O.; Hermine, O.; Damaj, G. (2012). "Mast cell leukemia". Blood. 121 (8): 1285–1295. doi:10.1182/blood-2012-07-442400. ISSN 0006-4971.
- ↑ 3.0 3.1 Kristensen, Thomas; Vestergaard, Hanne; Møller, Michael Boe (2011). "Improved Detection of the KIT D816V Mutation in Patients with Systemic Mastocytosis Using a Quantitative and Highly Sensitive Real-Time qPCR Assay". The Journal of Molecular Diagnostics. 13 (2): 180–188. doi:10.1016/j.jmoldx.2010.10.004. ISSN 1525-1578.
- ↑ 4.0 4.1 Horvai AE, Link TM. Bone and Soft Tissue Pathology. Elsevier Health Sciences (2012). http://books.google.com?id=p2DV6VWdXx8C. Accessed on November 30, 2015.
- ↑ 5.0 5.1 Valent, P.; Sotlar, K.; Sperr, W. R.; Escribano, L.; Yavuz, S.; Reiter, A.; George, T. I.; Kluin-Nelemans, H. C.; Hermine, O.; Butterfield, J. H.; Hagglund, H.; Ustun, C.; Hornick, J. L.; Triggiani, M.; Radia, D.; Akin, C.; Hartmann, K.; Gotlib, J.; Schwartz, L. B.; Verstovsek, S.; Orfao, A.; Metcalfe, D. D.; Arock, M.; Horny, H.- P. (2014). "Refined diagnostic criteria and classification of mast cell leukemia (MCL) and myelomastocytic leukemia (MML): a consensus proposal". Annals of Oncology. 25 (9): 1691–1700. doi:10.1093/annonc/mdu047. ISSN 0923-7534.
- ↑ 6.0 6.1 Jawhar, Mohamad; Schwaab, Juliana; Meggendorfer, Manja; Naumann, Nicole; Horny, Hans-Peter; Sotlar, Karl; Haferlach, Torsten; Schmitt, Karla; Fabarius, Alice; Valent, Peter; Hofmann, Wolf-Karsten; Cross, Nicholas C.P.; Metzgeroth, Georgia; Reiter, Andreas (2017). "The clinical and molecular diversity of mast cell leukemia with or without associated hematologic neoplasm". Haematologica. 102 (6): 1035–1043. doi:10.3324/haematol.2017.163964. ISSN 0390-6078.
- ↑ Image of peripheral blood smear of acute mast cell leukemia. Wikipedia (2015). https://en.wikipedia.org/wiki/Mast_cell_leukemia. Accessed on December 2, 2015