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A Review of Genetic Abnormalities in Unicentric and Multicentric Castleman Disease
SIMPLE SUMMARY: Castleman disease is a rare hematopoietic disorder with a broad spectrum of clinical presentations. Different subtypes have been described based on how many lymph nodes are involved, histologic appearance, and associated viral infections. Recently, significant molecular and genetic a...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063830/ https://www.ncbi.nlm.nih.gov/pubmed/33804823 http://dx.doi.org/10.3390/biology10040251 |
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author | Butzmann, Alexandra Kumar, Jyoti Sridhar, Kaushik Gollapudi, Sumanth Ohgami, Robert S. |
author_facet | Butzmann, Alexandra Kumar, Jyoti Sridhar, Kaushik Gollapudi, Sumanth Ohgami, Robert S. |
author_sort | Butzmann, Alexandra |
collection | PubMed |
description | SIMPLE SUMMARY: Castleman disease is a rare hematopoietic disorder with a broad spectrum of clinical presentations. Different subtypes have been described based on how many lymph nodes are involved, histologic appearance, and associated viral infections. Recently, significant molecular and genetic abnormalities associated with Castleman disease have been described. However, we continue to lack a framework of the biological mechanisms driving this disease process. Thus, our aim was to review all published cases of Castleman disease to date that described molecular abnormalities and correlate cytogenetic, molecular, and genetic alterations with disease subtypes. Our comprehensive review identifies subtype-specific and novel pathways which may allow for more targeted treatment options and unique biologic therapies for Castleman disease. ABSTRACT: Castleman disease (CD) is a rare lymphoproliferative disorder known to represent at least four distinct clinicopathologic subtypes. Large advancements in our clinical and histopathologic description of these diverse diseases have been made, resulting in subtyping based on number of enlarged lymph nodes (unicentric versus multicentric), according to viral infection by human herpes virus 8 (HHV-8) and human immunodeficiency virus (HIV), and with relation to clonal plasma cells (POEMS). In recent years, significant molecular and genetic abnormalities associated with CD have been described. However, we continue to lack a foundational understanding of the biological mechanisms driving this disease process. Here, we review all cases of CD with molecular abnormalities described in the literature to date, and correlate cytogenetic, molecular, and genetic abnormalities with disease subtypes and phenotypes. Our review notes complex karyotypes in subsets of cases, specific mutations in PDGFRB N666S in 10% of unicentric CD (UCD) and NCOA4 L261F in 23% of idiopathic multicentric CD (iMCD) cases. Genes affecting chromatin organization and abnormalities in methylation are seen more commonly in iMCD while abnormalities within the mitogen-activated protein kinase (MAPK) and interleukin signaling pathways are more frequent in UCD. Interestingly, there is a paucity of genetic studies evaluating HHV-8 positive multicentric CD (HHV-8+ MCD) and POEMS-associated CD. Our comprehensive review of genetic and molecular abnormalities in CD identifies subtype-specific and novel pathways which may allow for more targeted treatment options and unique biologic therapies. |
format | Online Article Text |
id | pubmed-8063830 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-80638302021-04-24 A Review of Genetic Abnormalities in Unicentric and Multicentric Castleman Disease Butzmann, Alexandra Kumar, Jyoti Sridhar, Kaushik Gollapudi, Sumanth Ohgami, Robert S. Biology (Basel) Review SIMPLE SUMMARY: Castleman disease is a rare hematopoietic disorder with a broad spectrum of clinical presentations. Different subtypes have been described based on how many lymph nodes are involved, histologic appearance, and associated viral infections. Recently, significant molecular and genetic abnormalities associated with Castleman disease have been described. However, we continue to lack a framework of the biological mechanisms driving this disease process. Thus, our aim was to review all published cases of Castleman disease to date that described molecular abnormalities and correlate cytogenetic, molecular, and genetic alterations with disease subtypes. Our comprehensive review identifies subtype-specific and novel pathways which may allow for more targeted treatment options and unique biologic therapies for Castleman disease. ABSTRACT: Castleman disease (CD) is a rare lymphoproliferative disorder known to represent at least four distinct clinicopathologic subtypes. Large advancements in our clinical and histopathologic description of these diverse diseases have been made, resulting in subtyping based on number of enlarged lymph nodes (unicentric versus multicentric), according to viral infection by human herpes virus 8 (HHV-8) and human immunodeficiency virus (HIV), and with relation to clonal plasma cells (POEMS). In recent years, significant molecular and genetic abnormalities associated with CD have been described. However, we continue to lack a foundational understanding of the biological mechanisms driving this disease process. Here, we review all cases of CD with molecular abnormalities described in the literature to date, and correlate cytogenetic, molecular, and genetic abnormalities with disease subtypes and phenotypes. Our review notes complex karyotypes in subsets of cases, specific mutations in PDGFRB N666S in 10% of unicentric CD (UCD) and NCOA4 L261F in 23% of idiopathic multicentric CD (iMCD) cases. Genes affecting chromatin organization and abnormalities in methylation are seen more commonly in iMCD while abnormalities within the mitogen-activated protein kinase (MAPK) and interleukin signaling pathways are more frequent in UCD. Interestingly, there is a paucity of genetic studies evaluating HHV-8 positive multicentric CD (HHV-8+ MCD) and POEMS-associated CD. Our comprehensive review of genetic and molecular abnormalities in CD identifies subtype-specific and novel pathways which may allow for more targeted treatment options and unique biologic therapies. MDPI 2021-03-24 /pmc/articles/PMC8063830/ /pubmed/33804823 http://dx.doi.org/10.3390/biology10040251 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ). |
spellingShingle | Review Butzmann, Alexandra Kumar, Jyoti Sridhar, Kaushik Gollapudi, Sumanth Ohgami, Robert S. A Review of Genetic Abnormalities in Unicentric and Multicentric Castleman Disease |
title | A Review of Genetic Abnormalities in Unicentric and Multicentric Castleman Disease |
title_full | A Review of Genetic Abnormalities in Unicentric and Multicentric Castleman Disease |
title_fullStr | A Review of Genetic Abnormalities in Unicentric and Multicentric Castleman Disease |
title_full_unstemmed | A Review of Genetic Abnormalities in Unicentric and Multicentric Castleman Disease |
title_short | A Review of Genetic Abnormalities in Unicentric and Multicentric Castleman Disease |
title_sort | review of genetic abnormalities in unicentric and multicentric castleman disease |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063830/ https://www.ncbi.nlm.nih.gov/pubmed/33804823 http://dx.doi.org/10.3390/biology10040251 |
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