Deficient Spindle Assembly Checkpoint in Multiple Myeloma

Multiple myeloma (MM) is a hematological disease characterized by an abnormal accumulation of plasma cells in the bone marrow. These cells have frequent cytogenetic abnormalities including translocations of the immunoglobulin heavy chain gene and chromosomal gains and losses. In fact, a singular cha...

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Main Authors:	Díaz-Rodríguez, Elena, Álvarez-Fernández, Stela, Chen, Xi, Paiva, Bruno, López-Pérez, Ricardo, García-Hernández, Juan Luis, San Miguel, Jesús F., Pandiella, Atanasio
Format:	Online
Language:	English
Published:	Public Library of Science 2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3223182/

id	pubmed-3223182
recordtype	oai_dc
spelling	pubmed-32231822011-11-30 Deficient Spindle Assembly Checkpoint in Multiple Myeloma Díaz-Rodríguez, Elena Álvarez-Fernández, Stela Chen, Xi Paiva, Bruno López-Pérez, Ricardo García-Hernández, Juan Luis San Miguel, Jesús F. Pandiella, Atanasio Research Article Multiple myeloma (MM) is a hematological disease characterized by an abnormal accumulation of plasma cells in the bone marrow. These cells have frequent cytogenetic abnormalities including translocations of the immunoglobulin heavy chain gene and chromosomal gains and losses. In fact, a singular characteristic differentiating MM from other hematological malignancies is the presence of a high degree of aneuploidies. As chromosomal abnormalities can be generated by alterations in the spindle assembly checkpoint (SAC), the functionality of such checkpoint was tested in MM. When SAC components were analyzed in MM cell lines, the RNA levels of most of them were conserved. Nevertheless, the protein content of some key constituents was very low in several cell lines, as was the case of MAD2 or CDC20 in RPMI-8226 or RPMI-LR5 cells. The recovery of their cellular content did not substantially affect cell growth, but improved their ability to segregate chromosomes. Finally, SAC functionality was tested by challenging cells with agents disrupting microtubule dynamics. Most of the cell lines analyzed exhibited functional defects in this checkpoint. Based on the data obtained, alterations both in SAC components and their functionality have been detected in MM, pointing to this pathway as a potential target in MM treatment. Public Library of Science 2011-11-23 /pmc/articles/PMC3223182/ /pubmed/22132115 http://dx.doi.org/10.1371/journal.pone.0027583 Text en Diaz-Rodríguez et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Díaz-Rodríguez, Elena Álvarez-Fernández, Stela Chen, Xi Paiva, Bruno López-Pérez, Ricardo García-Hernández, Juan Luis San Miguel, Jesús F. Pandiella, Atanasio
spellingShingle	Díaz-Rodríguez, Elena Álvarez-Fernández, Stela Chen, Xi Paiva, Bruno López-Pérez, Ricardo García-Hernández, Juan Luis San Miguel, Jesús F. Pandiella, Atanasio Deficient Spindle Assembly Checkpoint in Multiple Myeloma
author_facet	Díaz-Rodríguez, Elena Álvarez-Fernández, Stela Chen, Xi Paiva, Bruno López-Pérez, Ricardo García-Hernández, Juan Luis San Miguel, Jesús F. Pandiella, Atanasio
author_sort	Díaz-Rodríguez, Elena
title	Deficient Spindle Assembly Checkpoint in Multiple Myeloma
title_short	Deficient Spindle Assembly Checkpoint in Multiple Myeloma
title_full	Deficient Spindle Assembly Checkpoint in Multiple Myeloma
title_fullStr	Deficient Spindle Assembly Checkpoint in Multiple Myeloma
title_full_unstemmed	Deficient Spindle Assembly Checkpoint in Multiple Myeloma
title_sort	deficient spindle assembly checkpoint in multiple myeloma
description	Multiple myeloma (MM) is a hematological disease characterized by an abnormal accumulation of plasma cells in the bone marrow. These cells have frequent cytogenetic abnormalities including translocations of the immunoglobulin heavy chain gene and chromosomal gains and losses. In fact, a singular characteristic differentiating MM from other hematological malignancies is the presence of a high degree of aneuploidies. As chromosomal abnormalities can be generated by alterations in the spindle assembly checkpoint (SAC), the functionality of such checkpoint was tested in MM. When SAC components were analyzed in MM cell lines, the RNA levels of most of them were conserved. Nevertheless, the protein content of some key constituents was very low in several cell lines, as was the case of MAD2 or CDC20 in RPMI-8226 or RPMI-LR5 cells. The recovery of their cellular content did not substantially affect cell growth, but improved their ability to segregate chromosomes. Finally, SAC functionality was tested by challenging cells with agents disrupting microtubule dynamics. Most of the cell lines analyzed exhibited functional defects in this checkpoint. Based on the data obtained, alterations both in SAC components and their functionality have been detected in MM, pointing to this pathway as a potential target in MM treatment.
publisher	Public Library of Science
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3223182/
_version_	1611489759869272064

Deficient Spindle Assembly Checkpoint in Multiple Myeloma

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