Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Kalff, A, Spencer, A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2012
Materias:
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
_version_ 1782245110995484672
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
work_keys_str_mv AT kalffa thet414translocationandfgfr3overexpressioninmultiplemyelomaprognosticimplicationsandcurrentclinicalstrategies
AT spencera thet414translocationandfgfr3overexpressioninmultiplemyelomaprognosticimplicationsandcurrentclinicalstrategies
AT kalffa t414translocationandfgfr3overexpressioninmultiplemyelomaprognosticimplicationsandcurrentclinicalstrategies
AT spencera t414translocationandfgfr3overexpressioninmultiplemyelomaprognosticimplicationsandcurrentclinicalstrategies