Ku70 is Associated with the Frequency of Chromosome Translocation in Human Lymphocytes After Radiation and T-Cell Acute Lymphoblastic Leukemia

Background: Chromosome translocation is one of the most common chromosomal causes to T-cell acute lymphoblastic leukemia (T-ALL). Ku70 is one of the key factors of error-prone DNA repair that may end in translocation. So far, the direct correlation between Ku70 and translocation has not been assessed. Our study aimed to investigate the association of Ku70 and translocation in human lymphocytes after radiation and T-ALL. Methods: Peripheral blood lymphocytes (PBLs) from volunteers and human lymphocyte cell line AHH-1were irradiated with X-rays to form chromosome translocations. The frequency of translocation was detected by fluorescence in situ hybridization (FISH), meanwhile, the expression of Ku70 was also detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot. Furthermore, Ku70 interference, overexpression and chemical inhibition were used in AHH-1 cell lines to confirm the correlation. Finally, we detected the expression of Ku70 in T-ALL samples with or without translocation. Results: Expression of Ku70 and frequencies of translocation were both significantly increased in PBLs after irradiated by X-rays, and a positive correlation between the expression (both mRNA and protein level) of Ku70 and the frequency of translocation was detected (r = 0.4877, P = 0.004; r = 0.3038, P = 0.0358 respectively). Moreover, Ku70 interference decreased the frequency of translocations while the frequency of translocations was not significantly affected after Ku70 overexpression. The expression of Ku70 and frequencies of translocation were both significantly increased in cells after irradiated combined with chemical inhibition (P <0.01). The protein level and mRNA level of Ku70 in T-ALL with translocation were significantly higher than T-ALL with normal karyotype (P = 0.009, P = 0.049 respectively). Conclusions: Ku70 is closely associated with the frequency of chromosome translocation in human lymphocytes after radiation and T-ALL. Ku70 might be a radiation damage biomarker and a potential tumor therapy target.