PT  - JOURNAL ARTICLE
AU  - SONODA, YURI
AU  - ITOH, MAI
AU  - TOHDA, SHUJI
TI  - Effects of HOXA9 Inhibitor DB818 on the Growth of Acute Myeloid Leukaemia Cells
AID  - 10.21873/anticanres.14950
DP  - 2021 Apr 01
TA  - Anticancer Research
PG  - 1841--1847
VI  - 41
IP  - 4
4099  - http://ar.iiarjournals.org/content/41/4/1841.short
4100  - http://ar.iiarjournals.org/content/41/4/1841.full
SO  - Anticancer Res2021 Apr 01; 41
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.