PMID- 28666010
OWN - NLM
STAT- MEDLINE
DCOM- 20171002
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 6
DP  - 2017
TI  - Dysregulation of H/ACA ribonucleoprotein components in chronic lymphocytic 
      leukemia.
PG  - e0179883
LID - 10.1371/journal.pone.0179883 [doi]
LID - e0179883
AB  - Telomeres are protective repeats of TTAGGG sequences located at the end of human 
      chromosomes. They are essential to maintain chromosomal integrity and genome 
      stability. Telomerase is a ribonucleoprotein complex containing an internal RNA 
      template (hTR) and a catalytic subunit (hTERT). The human hTR gene consists of 
      three major domains; among them the H/ACA domain is essential for telomere 
      biogenesis. H/ACA ribonucleoprotein (RNP) complex is composed of four 
      evolutionary conserved proteins, including dyskerin (encoded by DKC1 gene), 
      NOP10, NHP2 and GAR1. In this study, we have evaluated the expression profile of 
      the H/ACA RNP complex genes: DKC1, NOP10, NHP2 and GAR1, as well as hTERT and hTR 
      mRNA levels, in patients with chronic lymphocytic leukemia (CLL). Results were 
      correlated with the number and type of genetic alteration detected by 
      conventional cytogenetics and FISH (fluorescence in situ hybridization), IGHV 
      (immunoglobulin heavy chain variable region) mutational status, telomere length 
      (TL) and clinico-pathological characteristics of patients. Our results showed 
      significant decreased expression of GAR1, NOP10, DKC1 and hTR, as well as 
      increased mRNA levels of hTERT in patients compared to controls (p</=0.04). A 
      positive correlation between the expression of GAR1-NHP2, GAR1-NOP10, and 
      NOP10-NHP2 (p<0.0001), were observed. The analysis taking into account prognostic 
      factors showed a significant increased expression of hTERT gene in unmutated-IGHV 
      cases compared to mutated-CLL patients (p = 0.0185). The comparisons among FISH 
      groups exhibited increased expression of DKC1 in cases with two or more 
      alterations with respect to no abnormalities, trisomy 12 and del13q14, and of 
      NHP2 and NOP10 compared to those with del13q14 (p = 0.03). The analysis according 
      to TL showed a significant increased expression of hTERT (p = 0.0074) and DKC1 (p 
      = 0.0036) in patients with short telomeres compared to those with long TL. No 
      association between gene expression and clinical parameters was found. Our 
      results suggest a role for these telomere associated genes in genomic instability 
      and telomere dysfunction in CLL.
FAU - Dos Santos, Patricia Carolina
AU  - Dos Santos PC
AUID- ORCID: 0000-0002-6607-7620
AD  - Laboratorio de Genetica de Neoplasias Linfoides, Instituto de Medicina 
      Experimental, CONICET-Academia Nacional de Medicina, Buenos Aires, Argentina.
FAU - Panero, Julieta
AU  - Panero J
AD  - Laboratorio de Genetica de Neoplasias Linfoides, Instituto de Medicina 
      Experimental, CONICET-Academia Nacional de Medicina, Buenos Aires, Argentina.
FAU - Stanganelli, Carmen
AU  - Stanganelli C
AD  - Division Patologia Molecular, Instituto de Investigaciones Hematologicas-Academia 
      Nacional de Medicina, Buenos Aires, Argentina.
FAU - Palau Nagore, Virginia
AU  - Palau Nagore V
AD  - Laboratorio de Genetica de Neoplasias Linfoides, Instituto de Medicina 
      Experimental, CONICET-Academia Nacional de Medicina, Buenos Aires, Argentina.
FAU - Stella, Flavia
AU  - Stella F
AD  - Laboratorio de Genetica de Neoplasias Linfoides, Instituto de Medicina 
      Experimental, CONICET-Academia Nacional de Medicina, Buenos Aires, Argentina.
FAU - Bezares, Raimundo
AU  - Bezares R
AD  - Servicio de Hematologia, Hospital Teodoro Alvarez, Buenos Aires, Argentina.
FAU - Slavutsky, Irma
AU  - Slavutsky I
AD  - Laboratorio de Genetica de Neoplasias Linfoides, Instituto de Medicina 
      Experimental, CONICET-Academia Nacional de Medicina, Buenos Aires, Argentina.
LA  - eng
PT  - Journal Article
DEP - 20170630
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Ribonucleoproteins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Female
MH  - Gene Expression Profiling
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/genetics/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Real-Time Polymerase Chain Reaction
MH  - Ribonucleoproteins/*metabolism
MH  - Telomere
PMC - PMC5493334
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2017/07/01 06:00
MHDA- 2017/10/03 06:00
PMCR- 2017/06/30
CRDT- 2017/07/01 06:00
PHST- 2017/01/26 00:00 [received]
PHST- 2017/06/06 00:00 [accepted]
PHST- 2017/07/01 06:00 [entrez]
PHST- 2017/07/01 06:00 [pubmed]
PHST- 2017/10/03 06:00 [medline]
PHST- 2017/06/30 00:00 [pmc-release]
AID - PONE-D-17-03532 [pii]
AID - 10.1371/journal.pone.0179883 [doi]
PST - epublish
SO  - PLoS One. 2017 Jun 30;12(6):e0179883. doi: 10.1371/journal.pone.0179883. 
      eCollection 2017.