Low-dose Decitabine Enhances Chidamide-Induced Apoptosis in Adult Acute Lymphoblast Leukemia, Especially for p16-Deleted Patients Through DNA Damage

Abstract

Aim: To investigate the combined action of decitabine (DAC) with chidamide (CS055) on acute lymphoblastic leukemia (ALL) cells. Materials & methods: ALL cell lines as well as primary cells from 17 ALL patients were subjected to different treatments and thereafter cell counting Kit-8 (CCK-8) assay, flow cytometry and western blot were employed to determine IC₅₀, apoptosis and checkpoint kinase 1 and γH2A.X expression. Results: Low-dose DAC combined with CS055 could effectively kill ALL cells by the reduction of cell viability and induction of apoptosis. This was also observed in primary cells from 17 ALL patients, especially for those with p16 gene deletion. Suppression of checkpoint kinase 1 phosphorylation and upregulation of γH2A.X expression was demonstrated to participate in DAC plus CS055-induced apoptosis. Conclusion: Low-dose DAC could enhance chidamide-induced apoptosis in adult ALL, especially for patients with p16 gene deletion through DNA damage.

Keywords::

• acute lymphoblastic leukemia
• apoptosis
• chidamide
• decitabine
• DNA damage
• p16 gene

Financial & competing interests disclosure

This work is financially supported by Science and Technology Program of Guangzhou, China (201607010072), Medical Innovation Program of Fujian Province, PR China (2016-CXB-7) and Natural Science Foundation of Guangdong Province, China (2014A030313280). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work is financially supported by Science and Technology Program of Guangzhou, China (201607010072), Medical Innovation Program of Fujian Province, PR China (2016-CXB-7) and Natural Science Foundation of Guangdong Province, China (2014A030313280). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.