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Molecular Landscapes and Models of Acute Erythroleukemia

Malignancies of the erythroid lineage are rare but aggressive diseases. Notably, the first insights into their biology emerged over half a century ago from avian and murine tumor viruses-induced erythroleukemia models providing the rationale for several transgenic mouse models that unraveled the tra...

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Autores principales: Fagnan, Alexandre, Piqué-Borràs, Maria-Riera, Tauchmann, Samantha, Mercher, Thomas, Schwaller, Juerg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061683/
https://www.ncbi.nlm.nih.gov/pubmed/33898929
http://dx.doi.org/10.1097/HS9.0000000000000558
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author Fagnan, Alexandre
Piqué-Borràs, Maria-Riera
Tauchmann, Samantha
Mercher, Thomas
Schwaller, Juerg
author_facet Fagnan, Alexandre
Piqué-Borràs, Maria-Riera
Tauchmann, Samantha
Mercher, Thomas
Schwaller, Juerg
author_sort Fagnan, Alexandre
collection PubMed
description Malignancies of the erythroid lineage are rare but aggressive diseases. Notably, the first insights into their biology emerged over half a century ago from avian and murine tumor viruses-induced erythroleukemia models providing the rationale for several transgenic mouse models that unraveled the transforming potential of signaling effectors and transcription factors in the erythroid lineage. More recently, genetic roadmaps have fueled efforts to establish models that are based on the epigenomic lesions observed in patients with erythroid malignancies. These models, together with often unexpected erythroid phenotypes in genetically modified mice, provided further insights into the molecular mechanisms of disease initiation and maintenance. Here, we review how the increasing knowledge of human erythroleukemia genetics combined with those from various mouse models indicate that the pathogenesis of the disease is based on the interplay between signaling mutations, impaired TP53 function, and altered chromatin organization. These alterations lead to aberrant activity of erythroid transcriptional master regulators like GATA1, indicating that erythroleukemia will most likely require combinatorial targeting for efficient therapeutic interventions.
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spelling pubmed-80616832021-04-23 Molecular Landscapes and Models of Acute Erythroleukemia Fagnan, Alexandre Piqué-Borràs, Maria-Riera Tauchmann, Samantha Mercher, Thomas Schwaller, Juerg Hemasphere Review Article Malignancies of the erythroid lineage are rare but aggressive diseases. Notably, the first insights into their biology emerged over half a century ago from avian and murine tumor viruses-induced erythroleukemia models providing the rationale for several transgenic mouse models that unraveled the transforming potential of signaling effectors and transcription factors in the erythroid lineage. More recently, genetic roadmaps have fueled efforts to establish models that are based on the epigenomic lesions observed in patients with erythroid malignancies. These models, together with often unexpected erythroid phenotypes in genetically modified mice, provided further insights into the molecular mechanisms of disease initiation and maintenance. Here, we review how the increasing knowledge of human erythroleukemia genetics combined with those from various mouse models indicate that the pathogenesis of the disease is based on the interplay between signaling mutations, impaired TP53 function, and altered chromatin organization. These alterations lead to aberrant activity of erythroid transcriptional master regulators like GATA1, indicating that erythroleukemia will most likely require combinatorial targeting for efficient therapeutic interventions. Lippincott Williams & Wilkins 2021-04-21 /pmc/articles/PMC8061683/ /pubmed/33898929 http://dx.doi.org/10.1097/HS9.0000000000000558 Text en Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Hematology Association. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY) (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Fagnan, Alexandre
Piqué-Borràs, Maria-Riera
Tauchmann, Samantha
Mercher, Thomas
Schwaller, Juerg
Molecular Landscapes and Models of Acute Erythroleukemia
title Molecular Landscapes and Models of Acute Erythroleukemia
title_full Molecular Landscapes and Models of Acute Erythroleukemia
title_fullStr Molecular Landscapes and Models of Acute Erythroleukemia
title_full_unstemmed Molecular Landscapes and Models of Acute Erythroleukemia
title_short Molecular Landscapes and Models of Acute Erythroleukemia
title_sort molecular landscapes and models of acute erythroleukemia
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061683/
https://www.ncbi.nlm.nih.gov/pubmed/33898929
http://dx.doi.org/10.1097/HS9.0000000000000558
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