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Expression of Shelterin component POT1 is associated with decreased telomere
length and immunity condition in humans with severe aplastic anemia
#MMPMID24892036
Wang T
; Mei SC
; Fu R
; Wang HQ
; Shao ZH
J Immunol Res
2014[]; 2014
(?): 439530
PMID24892036
show ga
Abnormal telomere attrition has been found to be closely related to patients with
SAA in recent years. To identify the incidence of telomere attrition in SAA
patients and investigate the relationship of telomere length with clinical
parameters, SAA patients (n=27) and healthy controls (n=15) were enrolled in this
study. Telomere length of PWBCs was significantly shorter in SAA patients than in
controls. Analysis of gene expression of Shelterin complex revealed markedly low
levels of POT1 expression in SAA groups relative to controls. No differences in
the gene expression of the other Shelterin components-TRF1, TRF2, TIN2, TPP1, and
RAP1-were identified. Addition of IFN-? to culture media induced a similar fall
in POT1 expression in bone marrow cells to that observed in cells cultured in the
presence of SAA serum, suggesting IFN-? is the agent responsible for this effect
of SAA serum. Furthermore, ATR, phosphorylated ATR, and phosphorylated ATM/ATR
substrate were all found similarly increased in bone marrow cells exposed to SAA
serum, TNF-?, or IFN-?. In summary, SAA patients have short telomeres and
decreased POT1 expression. TNF-? and IFN-? are found at high concentrations in
SAA patients and may be the effectors that trigger apoptosis through POT1 and
ATR.