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The t(4;14) translocation and FGFR3 overexpression in multiple myeloma: prognostic implications and current clinical strategies
Multiple myeloma (MM) is a heterogeneous plasma cell disorder characterized by genetic abnormalities, including chromosomal translocations, deletions, duplications and genetic mutations. Translocations involving the immunoglobulin heavy chain region at chromosome 14q32 are observed in approximately...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2012
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461707/ https://www.ncbi.nlm.nih.gov/pubmed/22961061 http://dx.doi.org/10.1038/bcj.2012.37 |
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author | Kalff, A Spencer, A |
author_facet | Kalff, A Spencer, A |
author_sort | Kalff, A |
collection | PubMed |
description | Multiple myeloma (MM) is a heterogeneous plasma cell disorder characterized by genetic abnormalities, including chromosomal translocations, deletions, duplications and genetic mutations. Translocations involving the immunoglobulin heavy chain region at chromosome 14q32 are observed in approximately 40% of patients with MM. Translocation of oncogenes into this region may lead to their increased expression, contributing to disease initiation, disease progression and therapeutic resistance. The t(4;14) translocation is associated with upregulation of the fibroblast growth factor receptor 3 (FGFR3) and the myeloma SET domain protein. Patients with t(4;14) demonstrate an overall poor prognosis that is only partially mitigated by the use of the novel agents bortezomib and lenalidomide; as such, an unmet medical need remains for patients with this aberration. Preclinical studies of inhibitors of FGFR3 have shown promise in t(4;14) MM, and these studies have led to the initiation of clinical trials. Data from these trials will help to determine the clinical utility of FGFR3 inhibitors for patients with t(4;14) MM and may pave the way for personalized medicine in patients with this incurable disease. |
format | Online Article Text |
id | pubmed-3461707 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-34617072012-10-03 The t(4;14) translocation and FGFR3 overexpression in multiple myeloma: prognostic implications and current clinical strategies Kalff, A Spencer, A Blood Cancer J Review Multiple myeloma (MM) is a heterogeneous plasma cell disorder characterized by genetic abnormalities, including chromosomal translocations, deletions, duplications and genetic mutations. Translocations involving the immunoglobulin heavy chain region at chromosome 14q32 are observed in approximately 40% of patients with MM. Translocation of oncogenes into this region may lead to their increased expression, contributing to disease initiation, disease progression and therapeutic resistance. The t(4;14) translocation is associated with upregulation of the fibroblast growth factor receptor 3 (FGFR3) and the myeloma SET domain protein. Patients with t(4;14) demonstrate an overall poor prognosis that is only partially mitigated by the use of the novel agents bortezomib and lenalidomide; as such, an unmet medical need remains for patients with this aberration. Preclinical studies of inhibitors of FGFR3 have shown promise in t(4;14) MM, and these studies have led to the initiation of clinical trials. Data from these trials will help to determine the clinical utility of FGFR3 inhibitors for patients with t(4;14) MM and may pave the way for personalized medicine in patients with this incurable disease. Nature Publishing Group 2012-09 2012-09-07 /pmc/articles/PMC3461707/ /pubmed/22961061 http://dx.doi.org/10.1038/bcj.2012.37 Text en Copyright © 2012 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-No Derivative Works 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Review Kalff, A Spencer, A The t(4;14) translocation and FGFR3 overexpression in multiple myeloma: prognostic implications and current clinical strategies |
title | The t(4;14) translocation and FGFR3 overexpression in multiple myeloma: prognostic implications and current clinical strategies |
title_full | The t(4;14) translocation and FGFR3 overexpression in multiple myeloma: prognostic implications and current clinical strategies |
title_fullStr | The t(4;14) translocation and FGFR3 overexpression in multiple myeloma: prognostic implications and current clinical strategies |
title_full_unstemmed | The t(4;14) translocation and FGFR3 overexpression in multiple myeloma: prognostic implications and current clinical strategies |
title_short | The t(4;14) translocation and FGFR3 overexpression in multiple myeloma: prognostic implications and current clinical strategies |
title_sort | t(4;14) translocation and fgfr3 overexpression in multiple myeloma: prognostic implications and current clinical strategies |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461707/ https://www.ncbi.nlm.nih.gov/pubmed/22961061 http://dx.doi.org/10.1038/bcj.2012.37 |
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