title: Deficient spindle assembly checkpoint in multiple myeloma.
abstract: 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.
authors: Instituto de Biología Molecular y Celular del Cáncer, CSIC-Universidad de Salamanca, Salamanca, Spain. ediaz@usal.es
authors: Elena
authors: E
authors: Díaz-Rodríguez
authors: Stela
authors: S
authors: Álvarez-Fernández
authors: Xi
authors: X
authors: Chen
authors: Bruno
authors: B
authors: Paiva
authors: Ricardo
authors: R
authors: López-Pérez
authors: Juan Luis
authors: JL
authors: García-Hernández
authors: Jesús F
authors: JF
authors: San Miguel
authors: Atanasio
authors: A
authors: Pandiella
mesh_terms: D000782:Aneuploidy; D002135:Calcium-Binding Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D042822:Genomic Instability / Q000187:drug effects; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000235:genetics; D064246:Mad2 Proteins; D009101:Multiple Myeloma / Q000235:genetics / Q000473:pathology*; D015739:Nocodazole / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D012190:Retroviridae / Q000187:drug effects / Q000235:genetics; D014161:Transduction, Genetic
chemical_list: D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D015739:Nocodazole