Expression profile of shelterin components in plasma cell disorders. Clinical significance of POT1 overexpression

Authors
Panero, Julieta; Stanganelli, Carmen; Arbelbide, Jorge; Fantl, Dorotea Beatriz; Kohan, Dana; Garcia Rivello, Hernan; Rabinovich, Gabriel Adrian; Slavutsky, Irma Rosa
Publication Year
2014
Language
English
Format
article
Status
Published version
Description
In this study we analyzed the expression profile and the interactions of all shelterin components in patients with MM and MGUS, and correlated the results with hTERT expression, telomere length (TL) and clinical characteristics of the diseases. Bone marrow samples of 154 patients: 70 with MGUS and 84 with MM were studied. Gene expression was determined by real-time quantitative RT-PCR and TL was evaluated by terminal restriction fragments. A significant overexpression of TRF2, POT1 and hTERT in MM compared to MGUS was observed (p<0.03). Due to the great heterogeneity in hTERT levels, patients were divided into three groups of expression: GI (low), GII (intermediate) and GIII (high). This classification showed an upregulation of TRF2 and RAP1 in MGUS (GIII vs. GI: p<0.01), and an increased expression of TRF2 and TPP1 in MM (GIII vs. GI and GII: p<0.04). In addition, a significant over-expression of LGALS1 (encoding galectin-1, a multifunctional β-galactoside binding protein) was observed in GII/III respect to GI (p=0.013). TL was inversely correlated with telomerase expression (GII vs. GI: p=0.02). In MM, POT1 were positively correlated with β2microglobulin (β2M), advanced DS stages, high calcium levels and bone lesions (p=0.009), whereas TL was correlated positively with hemoglobin levels and negatively with β2M (p=0.02). Our findings provide the first evidence of a global modification in the expression of the six shelterin subunits, their interactions and the correlation between hTERT and LSGAL1 in plasma cell disorders. The strong association of POT1 with different parameters of adverse clinical outcome suggests its importance as a target for novel therapeutic strategies.
Fil: Panero, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; Argentina
Fil: Stanganelli, Carmen. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "mariano R. Castex"; Argentina
Fil: Arbelbide, Jorge. Hospital Italiano de Buenos Aires; Argentina
Fil: Fantl, Dorotea Beatriz. Hospital Italiano de Buenos Aires; Argentina
Fil: Kohan, Dana. Hospital Italiano de Buenos Aires; Argentina
Fil: Garcia Rivello, Hernan. Hospital Italiano de Buenos Aires; Argentina
Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Slavutsky, Irma Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental; Argentina
Subject
MULTIPLE MYELOMA
MGUS
TELOMERE-ASSOCIATED GENES
POT1 EXPRESSION
Genética Humana
Medicina Básica
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Restricted access
License
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/7635