RT Journal Article SR Electronic T1 Effects of HOXA9 Inhibitor DB818 on the Growth of Acute Myeloid Leukaemia Cells JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 1841 OP 1847 DO 10.21873/anticanres.14950 VO 41 IS 4 A1 YURI SONODA A1 MAI ITOH A1 SHUJI TOHDA YR 2021 UL http://ar.iiarjournals.org/content/41/4/1841.abstract AB 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.