deficient spindle assembly checkpoint in multiple myeloma缺乏纺锤体组装在多发性骨髓瘤检查点.pdfVIP

Deficient Spindle Assembly Checkpoint in Multiple Myeloma ´ ´ 1 ´ ´ 1 1 1,2 ´ ´ 1 Elena Dıaz-Rodrıguez *, Stela Alvarez-Fernandez , Xi Chen , Bruno Paiva , Ricardo Lopez-Perez , Juan ´ ´ 1,2 ´ 1,2 1 Luis Garcıa-Hernandez , Jesus F. San Miguel , Atanasio Pandiella ´ ´ ´ 1 Instituto de Biologıa Molecular y Celular del Cancer, CSIC-Universidad de Salamanca, Salamanca, Spain, 2 Servicio de Hematologıa, Hospital Universitario de Salamanca, Salamanca, Spain 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 segrega