IP: Dr. Jesús San Miguel

Resumen del proyecto: Multiple myeloma is a malignant tumor of B-lineage hematopoietic cells, characterized by the clonal expansion of malignant plasma cells in the bone marrow. Novel treatments for this disease have improved the outcome of MM patients in the last few years. However, most patients relapse and MM is still considered an incurable disease with median survival ranging from three to five years.
Multiple myeloma is characterized by a marked genomic instability, leading to ploidy status alterations, deletions/amplifications, and chromosomal translocations involving the inmunoglobulin heavy-chain (IGH) locus at 14q32. The mechanism for this genetic instability is largely unknown, however it is considered responsible for disease appearance and progression, as it results in the alteration of different oncogenes. In the present project we will investigate two mechanisms that, if altered, would explain the accumulation of chromosomal abnormalities in MM cells: i) The repair of double strand breaks (DSBs) in the DNA, and ii) The activation of the mitotic checkpoint that arrest cells at G2M when injury to the mitotic machinery occurs. Kinetics of DSB repair and checkpoint activation in Multiple Mieloma cell lines will be analyzed and compared with the exhibited by immortalized B lymphocytes, that will be used as healthy controls. Our analysis will determine whether DNA repair or checkpoint activation are defective in MM cells.

Entidad financiadora: Instituto de Salus Carlos III