HDAC8 promotes daunorubicin resistance of human acute myeloid leukemia cells via regulation of IL-6 and IL-8

The chemoresistance is one of the major challenges for acute myeloid leukemia (AML) treatment. We found that the expression of histone deacetylase 8 (HDAC8) was increased in daunorubicin (DNR) resistant AML cells, while targeted inhibition of HDAC8 by its specific siRNA or inhibitor can restore sensitivity of DNR treatment. Further, targeted inhibition of HDAC8 can suppress expression of interleukin 6 (IL-6) and IL-8. While recombinant IL-6 (rIL-6) and rIL-8 can reverse si-HDAC8-resored DNR sensitivity of AML cells. Mechanistical study revealed that HDAC8 increased the expression of p65, one of key components of NF-kappa B complex, to promote the expression of IL-6 and IL-8. It might be due to that HDAC8 can directly bind with the promoter of p65 to increase its transcription and expres-sion. Collectively, our data suggested that HDAC8 promotes DNR resistance of human AML cells via regulation of IL-6and IL-8.

Automated summary

The increased expression of HDAC8 contributes to chemoresistance in AML by regulating IL-6 and IL-8. Targeted inhibition of HDAC8 can restore sensitivity of AML cells to DNR treatment.