title: Altered mRNA expression of telomere-associated genes in monoclonal gammopathy of undetermined significance and multiple myeloma.
abstract: In this study, we explored changes in the expression of the telomere maintenance genes, TRF1, TRF2 and TANK1 in patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). Results were correlated with human telomerase reverse transcriptase (hTERT ) expression, telomere length (TL) and clinicopathological characteristics. Bone marrow (BM) samples from 132 patients, 64 with MGUS and 68 with MM, were studied. Real-time quantitative reverse transcription-polymerase chain reaction was used to quantify gene expression. TL was evaluated by terminal restriction fragment length analysis. MGUS patients showed increased TRF1 levels (P = 0.006) and lower expression of TRF2 (P = 0.005) and TANK1 (P = 0.003) compared with MM patients. For hTERT analysis, patients were divided into three groups by use of receiver operating characteristics: low (group I [GI]), intermediate (group II [GII]) and high (group III [GIII]) expression. We observed increasing expression of TRF2 and TANK1 from GI to GIII in MGUS and MM, with differences for both genes in MM (P < 0.01) and for TRF2 in MGUS (P < 0.01). GIII patients with the highest telomerase expression had the shortest TL. In both entities, a positive association between TRF2-TANK1, TRF2-hTERT and TANK1-hTERT (P ≤ 0.01) was observed. In MM, the percentage of BM infiltration and Ki-67 index were positively associated with TRF2, TANK1 and hTERT expression (P ≤ 0.03) and negatively with TL (P = 0.02), whereas lactate dehydrogenase was significantly correlated with TRF2 mRNA (P = 0.008). Our findings provide the first evidence of a modification in the expression of telomeric proteins in plasma cell disorders, and suggest that mechanisms other than telomerase activation are involved in TL maintenance in these pathologies.
authors.affiliation: Departamento de Genética, Instituto de Investigaciones Hematológicas "Mariano R. Castex," Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: Julieta
authors.initials: J
authors.lastname: Panero
authors.forename: Jorge
authors.initials: J
authors.lastname: Arbelbide
authors.forename: Dorotea Beatriz
authors.initials: DB
authors.lastname: Fantl
authors.forename: Hernán García
authors.initials: HG
authors.lastname: Rivello
authors.forename: Dana
authors.initials: D
authors.lastname: Kohan
authors.forename: Irma
authors.initials: I
authors.lastname: Slavutsky
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics*; D010265:Paraproteinemias / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D038501:Tankyrases / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism; D035321:Telomeric Repeat Binding Protein 1 / Q000378:metabolism*; D035341:Telomeric Repeat Binding Protein 2 / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D038501:Tankyrases; D019098:Telomerase; D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; C504753:TERF2 protein, human; C418109:TNKS protein, human