Decreased Expression of Telomere Length Regulating Factors TRF1, and Tankyrase 1 in Patients with Adult Acute Leukemia.

Abstract

Telomeric repeat binding factor 1 (TRF1) and Tankyrase 1 (a human telomeric poly(ADP-ribose) polymerase) may play key roles in the maintenance of telomere function. TRF1 negatively regulates telomere elongation, while Tankyrase 1 acts as positive regulator of telomere length. In this study, we examined the expressions of TRF1 and Tankyrase 1 in 46 samples from patients with acute leukemia at diagnosis by quantitative reverse transcription real-time polymerase chain reaction and then analyzed the relation with the expression of protooncogene c-myc. TRF1 mRNAs were significantly down-regulated in patients with acute leukemia compared to controls. On the other hand, the mononuclear cells (MNCs) of patient with acute myelogenous leukemia (AML) expressed TRF1 at higher levels than that of patient with acute lymphoblastic leukemia (ALL) (p<0.01) or myelodysplastic syndrome (MDS). Compared to the patients with CD 34 negative AML, patients with CD34 positive AML expressed lower levels of TFR1 (p<0.01). The expression levels of Tankyrase 1 mRNA progressively decreased in patients with MDS, AML and ALL, although it was not significant. Moreover, there was a significantly correlation between the expression of TRF1 mRNA and Tankyrase 1 mRNA in AML cells (r = 0.394, p<0.01). Expression of c-myc mRNA was found gradually reduced in patients with AML, ALL and MDS. Otherwise, the expression level of TRF1 significantly correlated with those of c-myc in patients with AML(r=0.381, p=0.02) and CD34 positive AML (r=0.814, p<0.01). These results suggest that TRF1 gene expression in acute leukemia is down-regulation, and higher expression of TRF1 mRNA may be a reason for shorter telomere in some AML cells. There is dysfunction of TRF1 expression in the CD34 positive subset of AML. The patients with lower expression of TRF1 may have a poor prognostic.