Expression Expression profile of telomere-associated Genes in Multiple Myeloma

RAFAEL DÍAZ DE LA GUARDIA; PURIFICACIÓN CATALINA; JULIETA PANERO; CAROLINA ELOSUA; ANDRES PULGARIN; MARÍA BELÉN LÓPEZ; VERONICA AYLLON; GERTRUDIS LIGERO; IRMA SLAVUTSKY; PAOLA LEONE

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE (PRINT)

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Oxford; Año: 2012

1582-1838

In order to contribute further to the understanding of multiple myeloma, our interest is focused on determining the mechanisms by which tumor plasma cells have a higher survival than normal plasma cells, a possible mechanism for their accumulation in the bone marrow. In this paper, we study the expression profiles of the genes involved in regulation, inhibition, protection and telomere length maintenance, telomerase activity, and apoptosis in patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), multiple myeloma (MM) and plasma cell leukaemia (PCL), and human myeloma cell lines (HMCLs), using gene expression arrays and qPCR. By conventional cytogenetic and FISH, we identified a high number of telomeric associations (TAs) in patients and HMCLs. Telomere length by terminal restriction fragment (TRF) assay showed a mean TRF peak value shorter in patients and HMCLs, with a consistent correlation with the number of TAs. We found that 49 genes were differentially expressed between patients and HMCLs compared with controls. Sixteen of these genes were directly associated in telomere length maintenance, as well as hTERT. The genes are HSPA9, KRAS, RB1 and members of the families: Small nucleolar ribonucleoproteins, A/B subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins, and 14-3-3 family, genes involved in post-transcriptional and/or post-translational modification of hTERT, with higher expression levels than human embryonic stem cells lines (hESCs). In conclusion, multiple myeloma tumor cells maintain stable short telomere lengths without exceeding the short critical length, allowing cell division to continue.