Details

Autor(en) / Beteiligte

• Cao, Yang
• Liu, Yue
• Shang, Limei
• Wei, Wei
• Shen, Yangling
• Gu, Quan
• Xie, Xiaobao
• Dong, Weimin
• Lin, Yan
• Yue, Yanhua
• Wang, Fei
• Gu, Weiying

Titel

Decitabine and all-trans retinoic acid synergistically exhibit cytotoxicity against elderly AML patients via miR-34a/MYCN axis

Ist Teil von

• Biomedicine & pharmacotherapy, 2020-05, Vol.125, p.109878, Article 109878

Ort / Verlag

France: Elsevier Masson SAS

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• [Display omitted] •The combination of DAC and ATRA regimen exerted an antineoplastic effect in elderly AML patients ineligible for intensive induction therapy.•DAC and ATRA synergistically induced the growth inhibition and apoptosis of AML cells partially through miR-34a/MYCN axis.•DAC and ATRA inhibited DNMT1, epigenetically activated miR-34a and down-regulated its target MYCN. This study aimed to investigate the efficacy and mechanism of decitabine (DAC) and all-trans retinoic acid (ATRA) in elderly acute myeloid leukemia (AML) patients and cultured cells. Our clinical trial enrolled 36 elderly patients who were judged ineligible for conventional chemotherapy, receiving DAC and ATRA regimen (DAC 20 mg/m2 days 1–5; ATRA 20 mg/m2 days 4–28 in the first cycle and days 1–28 in the subsequent cycle). Treated with a median of 3 cycles (range 1–6), 44.4 % of patients achieved complete remission (CR), 11.1 % achieved CR with incomplete peripheral count recovery (CRi) and 13.9 % achieved partial remission (PR). The median overall survival (OS) was 12.1 months; the 1-year and 2-year OS rates were 49.6 % and 17.2 %. In addition, our in vitro studies indicated that the antineoplastic activities of DAC and ATRA mutually reinforced, which induced growth inhibition, cell cycle arrest and apoptosis of AML cells. Meanwhile, we found DAC and ATRA inhibited DNMT1, activated miR-34a via promoter hypomethylation, down-regulated its target MYCN and thus exerted a synergistic antineoplastic effect. In conclusion, DAC plus ATRA regimen might be effective and well-tolerated for elderly patients partially through modulating miR-34a/MYCN axis.