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...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2011-11, Vol.6 (11), p.e27583
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: Article
Language:English
Subjects:
Abnormalities
Aneuploidy
Apoptosis
Assembly
Biology
Biotechnology
Bone marrow
Calcium-Binding Proteins - metabolism
Cancer
Cell culture
Cell cycle
Cell Cycle Proteins - metabolism
Cell growth
Cell Line, Tumor
Chromosome translocations
Chromosomes
Gene expression
Gene Expression Regulation, Neoplastic - drug effects
Genes
Genomic Instability - drug effects
Hematology
Humans
Immunoglobulins
Kinases
M Phase Cell Cycle Checkpoints - genetics
Mad2 Proteins
Medicine
Multiple myeloma
Multiple Myeloma - genetics
Multiple Myeloma - pathology
Nocodazole - pharmacology
Plasma cells
Proteins
Repressor Proteins - metabolism
Retroviridae - drug effects
Retroviridae - genetics
Ribonucleic acid
RNA
RNA, Messenger - genetics
RNA, Messenger - metabolism
Signal transduction
Transduction, Genetic
Trends
Tumorigenesis
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0027583