Heme oxygenase (HO)-1 has anti-oxidative, anti-inflammatory, and anti-apoptotic 
activities. However, little is known about the regulation of HO-1 in human 
primary acute myeloid leukemia (AML) cells. Here we investigated the expression 
of HO-1 in primary and established AML cells as well as other types of leukemic 
cells and normal monocytes, and its regulatory mechanism by the transcriptional 
repressor, BTB and CNC homology 1 (Bach1), and the activator, nuclear factor 
erythroid-derived 2 related factor 2 (Nrf2). Leukemic cell lines such as U937 
expressed little HO-1, whereas most freshly isolated AML cells and monocytes 
expressed substantial amounts of HO-1, along with Bach1 and Nrf2. When U937 
cells were treated with phorbol myristate acetate (PHA) or gamma-interferon, 
they significantly expressed both HO-1 and Bach1, like primary AML cells. 
Treatment with lipopolysaccharide (LPS) enhanced HO-1 expression in U937 cells 
but suppressed it in primary monocytes and PMA-treated U937 cells. In 
HO-1-expressing cells, Bach1 was localized in the cytoplasm, but Nrf2 was 
localized in the nuclei. Chromatin immunoprecipitation assay of these cells 
revealed the preferential binding of Nrf2 over Bach1 to Maf-recognition 
elements, the enhancer regions of the HO-1 gene. The downregulation of the HO-1 
gene with siRNA increased a cytotoxic effect of an anticancer drug on primary 
AML cells, whereas the downregulation of Bach1 increased HO-1 expression, 
leading to enhanced survival. These and other results show that Bach1 plays a 
critical role in regulating HO-1 gene expression in AML cells and its expression 
suppresses their survival by downregulating HO-1 expression. Thus, functional 
upregulation of Bach1 is a potential strategy for antileukemic therapy.