Preclinical human models and emerging therapeutics for advanced systemic mastocytosis

Mastocytosis is a term used to denote a group of rare diseases characterized by an abnormal accumulation of neoplastic mast cells in various tissues and organs. In most patients with systemic mastocytosis, the neoplastic cells carry activating mutations in KIT. Progress in mastocytosis research has...

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Autores principales: Arock, Michel, Wedeh, Ghaith, Hoermann, Gregor, Bibi, Siham, Akin, Cem, Peter, Barbara, Gleixner, Karoline V., Hartmann, Karin, Butterfield, Joseph H., Metcalfe, Dean D., Valent, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ferrata Storti Foundation 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278969/
https://www.ncbi.nlm.nih.gov/pubmed/29976735
http://dx.doi.org/10.3324/haematol.2018.195867
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author Arock, Michel
Wedeh, Ghaith
Hoermann, Gregor
Bibi, Siham
Akin, Cem
Peter, Barbara
Gleixner, Karoline V.
Hartmann, Karin
Butterfield, Joseph H.
Metcalfe, Dean D.
Valent, Peter
author_facet Arock, Michel
Wedeh, Ghaith
Hoermann, Gregor
Bibi, Siham
Akin, Cem
Peter, Barbara
Gleixner, Karoline V.
Hartmann, Karin
Butterfield, Joseph H.
Metcalfe, Dean D.
Valent, Peter
author_sort Arock, Michel
collection PubMed
description Mastocytosis is a term used to denote a group of rare diseases characterized by an abnormal accumulation of neoplastic mast cells in various tissues and organs. In most patients with systemic mastocytosis, the neoplastic cells carry activating mutations in KIT. Progress in mastocytosis research has long been hindered by the lack of suitable in vitro models, such as permanent human mast cell lines. In fact, only a few human mast cell lines are available to date: HMC-1, LAD1/2, LUVA, ROSA and MCPV-1. The HMC-1 and LAD1/2 cell lines were derived from patients with mast cell leukemia. By contrast, the more recently established LUVA, ROSA and MCPV-1 cell lines were derived from CD34(+) cells of non-mastocytosis donors. While some of these cell lines (LAD1/2, LUVA, ROSA(KIT WT) and MCPV-1) do not harbor KIT mutations, HMC-1 and ROSA(KIT D816V) cells exhibit activating KIT mutations found in mastocytosis and have thus been used to study disease pathogenesis. In addition, these cell lines are increasingly employed to validate new therapeutic targets and to screen for effects of new targeted drugs. Recently, the ROSA(KIT D816V) subclone has been successfully used to generate a unique in vivo model of advanced mastocytosis by injection into immunocompromised mice. Such a model may allow in vivo validation of data obtained in vitro with targeted drugs directed against mastocytosis. In this review, we discuss the major characteristics of all available human mast cell lines, with particular emphasis on the use of HMC-1 and ROSA(KIT D816V) cells in preclinical therapeutic research in mastocytosis.
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spelling pubmed-62789692018-12-13 Preclinical human models and emerging therapeutics for advanced systemic mastocytosis Arock, Michel Wedeh, Ghaith Hoermann, Gregor Bibi, Siham Akin, Cem Peter, Barbara Gleixner, Karoline V. Hartmann, Karin Butterfield, Joseph H. Metcalfe, Dean D. Valent, Peter Haematologica Review Article Mastocytosis is a term used to denote a group of rare diseases characterized by an abnormal accumulation of neoplastic mast cells in various tissues and organs. In most patients with systemic mastocytosis, the neoplastic cells carry activating mutations in KIT. Progress in mastocytosis research has long been hindered by the lack of suitable in vitro models, such as permanent human mast cell lines. In fact, only a few human mast cell lines are available to date: HMC-1, LAD1/2, LUVA, ROSA and MCPV-1. The HMC-1 and LAD1/2 cell lines were derived from patients with mast cell leukemia. By contrast, the more recently established LUVA, ROSA and MCPV-1 cell lines were derived from CD34(+) cells of non-mastocytosis donors. While some of these cell lines (LAD1/2, LUVA, ROSA(KIT WT) and MCPV-1) do not harbor KIT mutations, HMC-1 and ROSA(KIT D816V) cells exhibit activating KIT mutations found in mastocytosis and have thus been used to study disease pathogenesis. In addition, these cell lines are increasingly employed to validate new therapeutic targets and to screen for effects of new targeted drugs. Recently, the ROSA(KIT D816V) subclone has been successfully used to generate a unique in vivo model of advanced mastocytosis by injection into immunocompromised mice. Such a model may allow in vivo validation of data obtained in vitro with targeted drugs directed against mastocytosis. In this review, we discuss the major characteristics of all available human mast cell lines, with particular emphasis on the use of HMC-1 and ROSA(KIT D816V) cells in preclinical therapeutic research in mastocytosis. Ferrata Storti Foundation 2018-11 /pmc/articles/PMC6278969/ /pubmed/29976735 http://dx.doi.org/10.3324/haematol.2018.195867 Text en Copyright© 2018 Ferrata Storti Foundation Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher.
spellingShingle Review Article
Arock, Michel
Wedeh, Ghaith
Hoermann, Gregor
Bibi, Siham
Akin, Cem
Peter, Barbara
Gleixner, Karoline V.
Hartmann, Karin
Butterfield, Joseph H.
Metcalfe, Dean D.
Valent, Peter
Preclinical human models and emerging therapeutics for advanced systemic mastocytosis
title Preclinical human models and emerging therapeutics for advanced systemic mastocytosis
title_full Preclinical human models and emerging therapeutics for advanced systemic mastocytosis
title_fullStr Preclinical human models and emerging therapeutics for advanced systemic mastocytosis
title_full_unstemmed Preclinical human models and emerging therapeutics for advanced systemic mastocytosis
title_short Preclinical human models and emerging therapeutics for advanced systemic mastocytosis
title_sort preclinical human models and emerging therapeutics for advanced systemic mastocytosis
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278969/
https://www.ncbi.nlm.nih.gov/pubmed/29976735
http://dx.doi.org/10.3324/haematol.2018.195867
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