ACER3 supports development of acute myeloid leukemia

Biochem Biophys Res Commun. 2016 Sep 9;478(1):33-38. doi: 10.1016/j.bbrc.2016.07.099. Epub 2016 Jul 25.

Abstract

No new therapy for acute myeloid leukemia (AML) has been approved for more than 30 years. To effectively treat AML, new molecular targets and therapeutic approaches must be identified. In silico analysis of several databases of AML patients demonstrated that the expression of alkaline ceramidase 3 (ACER3) significantly inversely correlates with the overall survival of AML patients. To determine whether ACER3 supports AML development, we employed an shRNA-encoding lentivirus system to inhibit acer3 expression in human AML cells including NB4, U937, and THP-1 cells. The ACER3 deficiency resulted in decreased cell growth and colony formation, elevated apoptosis, and lower AKT signaling of leukemia cells. Our study indicates that ACER3 contributes to AML pathogenesis, and suggests that alkaline ceramidase inhibition is an option to treat AML.

Keywords: Apoptosis; Ceramidase; Leukemia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Ceramidase / genetics*
  • Alkaline Ceramidase / metabolism
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation*
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / metabolism
  • Leukemia, Myeloid, Acute / pathology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Signal Transduction
  • Survival Analysis

Substances

  • RNA, Small Interfering
  • Proto-Oncogene Proteins c-akt
  • ACER3 protein, human
  • Alkaline Ceramidase