Expression Profile of Telomere-associated Genes in Multiple Myeloma

RAFAEL DÍAZ DE LA GUARDIA; PURIFICACIÓN CATALINA; JULIETA PANERO; CAROLINA ELOSUA; ANDRÉS PULGARIN; MARÍA BELÉN LÓPEZ; VERÓNICA AYLLÓN; GERTRUDIS LIGERO; IRMA SLAVUTSKY; PAOLA E. LEONE

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE (PRINT)

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2012

1582-1838

In order to further contribute to the understanding of multiple myeloma, we havefocused our research interests on the mechanisms by which tumor plasma cells have ahigher survival rate than normal plasma cells. In this paper, we study the expressionprofile of genes involved in the regulation and protection of telomere length, telomeraseactivity, and apoptosis in samples from patients with monoclonal gammopathy ofundetermined significance (MGUS), smoldering multiple myeloma (SMM), multiplemyeloma (MM) and plasma cell leukaemia (PCL), as well as several human myelomacell lines (HMCLs). By conventional cytogenetic and FISH studies, we identified a highnumber of telomeric associations (TAs). Moreover, telomere length measurements byterminal restriction fragment (TRF) assay showed a shorter mean TRF peak value, witha consistent correlation with the number of TAs. Using gene expression arrays andquantitative PCR we identified the hTERT gene together with sixteen other genesdirectly involved in telomere length maintenance: HSPA9, KRAS, RB1, members of theSmall nucleolar ribonucleoproteins family, A/B subfamily of ubiquitously expressedheterogeneous nuclear ribonucleoproteins, and 14-3-3 family. The expression levels ofthese genes was even higher than in human embryonic stem cells (hESCs) and inducedpluripotent stem cells (iPSCs), which have unlimited proliferation capacity. Inconclusion, the gene signature suggests that multiple myeloma tumor cells are able tomaintain stable short telomere lengths without exceeding the short critical length,allowing cell divisions to continue. We propose that this could be a mechanismcontributing to multiple myeloma tumor cells expansion in the bone marrow.