Ku70 affects the frequency of chromosome translocation in human lymphocytes after radiation and T-cell acute lymphoblastic leukemia

Zhenbo Cheng; Yupeng Wang; Lihuang Guo; Jiancheng Li; Wei Zhang; Conghui Zhang; Yangxu Liu; Yue Huang; Keqian Xu

doi:10.1186/s13014-022-02113-3

Ku70 affects the frequency of chromosome translocation in human lymphocytes after radiation and T-cell acute lymphoblastic leukemia

Radiat Oncol. 2022 Aug 19;17(1):144. doi: 10.1186/s13014-022-02113-3.

Authors

Zhenbo Cheng^{1

2}, Yupeng Wang³, Lihuang Guo^{1

2}, Jiancheng Li^{1

2}, Wei Zhang^{1

2}, Conghui Zhang^{1

2}, Yangxu Liu^{1

2}, Yue Huang^{1

2}, Keqian Xu^{4

5}

Affiliations

¹ Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, 410013, People's Republic of China.
² Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, 410013, People's Republic of China.
³ Department of Medical Laboratory, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, People's Republic of China.
⁴ Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, 410013, People's Republic of China. xukeqian@csu.edu.cn.
⁵ Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, 410013, People's Republic of China. xukeqian@csu.edu.cn.

Abstract

Background: As one of the most common chromosomal causes, chromosome translocation leads to T-cell acute lymphoblastic leukemia (T-ALL). Ku70 is one of the key factors of error-prone DNA repair and it may end in translocation. So far, the direct correlation between Ku70 and translocation has not been assessed. This study aimed to investigate the association between Ku70 and translocation in human lymphocytes after radiation and T-ALL.

Methods: Peripheral blood lymphocytes (PBLs) from volunteers and human lymphocyte cell line AHH-1 were irradiated with X-rays to form the chromosome translocations. Phytohemagglutinin (PHA) was used to stimulate lymphocytes. The frequency of translocation was detected by fluorescence in situ hybridization (FISH). Meanwhile, the expression of Ku70 was 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, the expression of Ku70 in T-ALL samples with or without translocation was detected.

Results: The expression of Ku70 and frequencies of translocation were both significantly increased in PBLs after being 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 irradiation, combined with chemical inhibition (P < 0.01). The protein level and mRNA level of Ku70 in T-ALL with translocation were obviously 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.

Keywords: Chromosome translocation; Human lymphocytes; Ku70; Radiation; Radiation damage biomarker; T-cell acute lymphoblastic leukemia; Therapy target.

MeSH terms

Humans
In Situ Hybridization, Fluorescence
Lymphocytes / radiation effects
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma*
RNA, Messenger
T-Lymphocytes
Translocation, Genetic*

Substances

RNA, Messenger

Abstract

MeSH terms

Substances

Grants and funding