Acute Myeloid Leukemia Telomerase Gene Mutation Study Sudden Changes In Telomere Length, Telomere Overhang

Background:Mutations in telomerase reverse transcriptase(TERT) and telomerase RNA component(TERC) can cause bone marrow failure. Recently these gene variants were also found in acute myeloid leukemia(AML) patients and appeared to account for the onset of the disease. Loss of telomerase function produces short telomeres and telometric overhangs, potentially resulting in chromosome instability. Investigations of telometric overhang were rare in the western country. None have been reported in China. In this study, we screened bone marrow samples from93patients with AML for variants in TERT and TERC genes and measured the length of both the telomere and overhang by Southern blot.Objectives:To study the incidence of TERC and TERT mutations in Chinese patients with AML and explore its relationship with telomere/overhang shortening. To measure length of both telomere and overhang and explore the relationship with disease prognosis.Results:One TERC and three TERT mutions were identified in93patients. The incidence of telomerase gene mutation in Chinese patients with AML is4.3%, which is lower than that of people in western countries. These people carrying TERC and TERT mutations have very short telomere, critical overhang and didn’t respond to the traditional chemotherapy as well. Majority of the patients had shorter telomere and overhang than the healthy controls. Patients with critical overhangs had poor prognosis.Conclusions:The incidence of telomerase gene mutation in Chinese patients with AML is4.3%. These patients with mutations had very short telomeres and critical overhangs compared with normal controls.Short overhang is an independent high risk of poor prognosis and is positively correlated with the disease severity.