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Recent Advances in the 5q- Syndrome
The 5q- syndrome is the most distinct of the myelodysplastic syndromes (MDS) and patients with this disorder have a deletion of chromosome 5q [del(5q)] as the sole karyotypic abnormality. Several genes mapping to the commonly deleted region of the 5q- syndrome have been implicated in disease pathoge...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Università Cattolica del Sacro Cuore
2015
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450650/ https://www.ncbi.nlm.nih.gov/pubmed/26075044 http://dx.doi.org/10.4084/MJHID.2015.037 |
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author | Pellagatti, Andrea Boultwood, Jacqueline |
author_facet | Pellagatti, Andrea Boultwood, Jacqueline |
author_sort | Pellagatti, Andrea |
collection | PubMed |
description | The 5q- syndrome is the most distinct of the myelodysplastic syndromes (MDS) and patients with this disorder have a deletion of chromosome 5q [del(5q)] as the sole karyotypic abnormality. Several genes mapping to the commonly deleted region of the 5q- syndrome have been implicated in disease pathogenesis in recent years. Haploinsufficiency of the ribosomal gene RPS14 has been shown to cause the erythroid defect in the 5q- syndrome. Loss of the microRNA genes miR-145 and miR-146a has been associated with the thrombocytosis observed in 5q- syndrome patients. Haploinsufficiency of CSNK1A1 leads to hematopoietic stem cell expansion in mice and may play a role in the initial clonal expansion in patients with 5q- syndrome. Moreover, a subset of patients harbor mutation of the remaining CSNK1A1 allele. Mouse models of the 5q- syndrome, which recapitulate the key features of the human disease, indicate that a p53-dependent mechanism underlies the pathophysiology of this disorder. Importantly, activation of p53 has been demonstrated in the human 5q- syndrome. Recurrent TP53 mutations have been associated with an increased risk of disease evolution and with decreased response to the drug lenalidomide in del(5q) MDS patients. Potential new therapeutic agents for del(5q) MDS include the translation enhancer L-leucine. |
format | Online Article Text |
id | pubmed-4450650 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Università Cattolica del Sacro Cuore |
record_format | MEDLINE/PubMed |
spelling | pubmed-44506502015-06-12 Recent Advances in the 5q- Syndrome Pellagatti, Andrea Boultwood, Jacqueline Mediterr J Hematol Infect Dis Review Article The 5q- syndrome is the most distinct of the myelodysplastic syndromes (MDS) and patients with this disorder have a deletion of chromosome 5q [del(5q)] as the sole karyotypic abnormality. Several genes mapping to the commonly deleted region of the 5q- syndrome have been implicated in disease pathogenesis in recent years. Haploinsufficiency of the ribosomal gene RPS14 has been shown to cause the erythroid defect in the 5q- syndrome. Loss of the microRNA genes miR-145 and miR-146a has been associated with the thrombocytosis observed in 5q- syndrome patients. Haploinsufficiency of CSNK1A1 leads to hematopoietic stem cell expansion in mice and may play a role in the initial clonal expansion in patients with 5q- syndrome. Moreover, a subset of patients harbor mutation of the remaining CSNK1A1 allele. Mouse models of the 5q- syndrome, which recapitulate the key features of the human disease, indicate that a p53-dependent mechanism underlies the pathophysiology of this disorder. Importantly, activation of p53 has been demonstrated in the human 5q- syndrome. Recurrent TP53 mutations have been associated with an increased risk of disease evolution and with decreased response to the drug lenalidomide in del(5q) MDS patients. Potential new therapeutic agents for del(5q) MDS include the translation enhancer L-leucine. Università Cattolica del Sacro Cuore 2015-05-20 /pmc/articles/PMC4450650/ /pubmed/26075044 http://dx.doi.org/10.4084/MJHID.2015.037 Text en This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Article Pellagatti, Andrea Boultwood, Jacqueline Recent Advances in the 5q- Syndrome |
title | Recent Advances in the 5q- Syndrome |
title_full | Recent Advances in the 5q- Syndrome |
title_fullStr | Recent Advances in the 5q- Syndrome |
title_full_unstemmed | Recent Advances in the 5q- Syndrome |
title_short | Recent Advances in the 5q- Syndrome |
title_sort | recent advances in the 5q- syndrome |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450650/ https://www.ncbi.nlm.nih.gov/pubmed/26075044 http://dx.doi.org/10.4084/MJHID.2015.037 |
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