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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Autores principales: Elena Díaz-Rodríguez, Stela Álvarez-Fernández, Xi Chen, Bruno Paiva, Ricardo López-Pérez, Juan Luis García-Hernández, Jesús F San Miguel, Atanasio Pandiella
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Publicado: Public Library of Science (PLoS) 2011
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Acceso en línea:https://doaj.org/article/525aefe7784b42099ba9f17f23b9e505
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spelling oai:doaj.org-article:525aefe7784b42099ba9f17f23b9e5052021-11-18T07:33:39ZDeficient spindle assembly checkpoint in multiple myeloma.1932-620310.1371/journal.pone.0027583https://doaj.org/article/525aefe7784b42099ba9f17f23b9e5052011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22132115/?tool=EBIhttps://doaj.org/toc/1932-6203Multiple 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.Elena Díaz-RodríguezStela Álvarez-FernándezXi ChenBruno PaivaRicardo López-PérezJuan Luis García-HernándezJesús F San MiguelAtanasio PandiellaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 11, p e27583 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Elena Díaz-Rodríguez
Stela Álvarez-Fernández
Xi Chen
Bruno Paiva
Ricardo López-Pérez
Juan Luis García-Hernández
Jesús F San Miguel
Atanasio Pandiella
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.
format article
author Elena Díaz-Rodríguez
Stela Álvarez-Fernández
Xi Chen
Bruno Paiva
Ricardo López-Pérez
Juan Luis García-Hernández
Jesús F San Miguel
Atanasio Pandiella
author_facet Elena Díaz-Rodríguez
Stela Álvarez-Fernández
Xi Chen
Bruno Paiva
Ricardo López-Pérez
Juan Luis García-Hernández
Jesús F San Miguel
Atanasio Pandiella
author_sort Elena Díaz-Rodríguez
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.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/525aefe7784b42099ba9f17f23b9e505
work_keys_str_mv AT elenadiazrodriguez deficientspindleassemblycheckpointinmultiplemyeloma
AT stelaalvarezfernandez deficientspindleassemblycheckpointinmultiplemyeloma
AT xichen deficientspindleassemblycheckpointinmultiplemyeloma
AT brunopaiva deficientspindleassemblycheckpointinmultiplemyeloma
AT ricardolopezperez deficientspindleassemblycheckpointinmultiplemyeloma
AT juanluisgarciahernandez deficientspindleassemblycheckpointinmultiplemyeloma
AT jesusfsanmiguel deficientspindleassemblycheckpointinmultiplemyeloma
AT atanasiopandiella deficientspindleassemblycheckpointinmultiplemyeloma
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