Effects of HOXA9 Inhibitor DB818 on the Growth of Acute Myeloid Leukaemia Cells

  • Anticancer Res. 2021 Apr;41(4):1841-1847. doi: 10.21873/anticanres.14950.
Yuri Sonoda  1 ,  Mai Itoh  1 ,  Shuji Tohda  2
Affiliations
  • 1. Department of Laboratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
  • 2. Department of Laboratory Medicine, Tokyo Medical and Dental University, Tokyo, Japan [email protected].
PMID: 33813389 DOI: 10.21873/anticanres.14950
Abstract

Background/aim: Homeobox A9 (HOXA9), a transcription factor regulating haematopoiesis and leukaemia cell proliferation, is suggested as a driver of acute myeloid leukaemia (AML). The aim of this study was to examine the effects of a synthetic HOXA9 inhibitor DB818 on AML cells in vitro.

Materials and methods: AML cell lines OCI/AML3, MV4-11, and THP-1 with gene mutations up-regulating HOXA9 expression were treated with DB818 and analysed for cell proliferation and gene expression. The effects of HOXA9 knockdown were also evaluated.

Results: In the three AML cell lines, DB818 suppressed growth, induced Apoptosis, and down-regulated the expression of HOXA9 transcriptional target genes: MYB proto-oncogene, transcription factor (MYB), MYC proto-oncogene, bHLH transcription factor (MYC), and BCL2 Apoptosis regulator (BCL2), while up-regulating that of Fos proto-oncogene, AP-1 transcription factor subunit (FOS). HOXA9 knockdown showed similar effects, except for MYC expression, which differed between DB818-treated and HOXA9-deficient OCI/AML3 cells, suggesting an off-target effect of DB818.

Conclusion: DB818 has potential as a novel molecular targeted drug for treating AML associated with HOXA9 overexpression.

Keywords
HOXA9; gene knockdown; inhibitor; leukaemia.
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