We used a degenerate RT-PCR screen and subsequent realtime quantitative RT-PCR assays to examine the expression of HOX and TALE-family genes in 34 cases of chromosomally defined AML for which outcome data were available. AMLs with favorable cytogenetic features were associated with low overall HOX gene expression whereas poor prognostic cases had high levels. Characteristically, multiple HOXA family members including HOXA3-HOXA10 were jointly overexpressed in conjunction with HOXB3, HOXB6, MEIS1 and PBX3. Higher levels of expression were also observed in the FAB subtype, AML-M1. Spearmann correlation coefficients indicated that the expression levels for many of these genes were highly interrelated. While we did not detect any significant correlations between HOX expression and complete response rates or age in this limited set of patients, there was a significant correlation between event-free survival and HOXA7 with a trend toward significance for HoxA9, HoxA4 and HoxA5. While patients with elevated HOX expression did worse, there were notable exceptions. Thus, although HOX overexpression and clinical resistance to chemotherapy often coincide, they are not inextricably linked. Our results indicate that quantitative HOX analysis has the potential to add new information to the management of patients with AML, especially where characteristic chromosomal alterations are lacking.

E-cadherin loss in cancer is associated with de-differentiation, invasion, and metastasis. Drosophila DE-cadherin is regulated by Wnt͞␤-catenin signaling, although this has not been demonstrated in mammalian cells. We previously reported that expression of WNT7a, encoded on 3p25, was frequently down-regulated in lung cancer, and that loss of E-cadherin or ␤-catenin was a poor prognostic feature. Here we show that WNT7a both activates E-cadherin expression via a ␤-catenin specific mechanism in lung cancer cells and is involved in a positive feedback loop. Li ؉ , a GSK3␤ inhibitor, led to E-cadherin induction in an inositol-independent manner. Similarly, exposure to mWNT7a specifically induced free ␤-catenin and E-cadherin. Among known transcriptional suppressors of E-cadherin, ZEB1 was uniquely correlated with E-cadherin loss in lung cancer cell lines, and its inhibition by RNA interference resulted in E-cadherin induction. Pharmacologic reversal of E-cadherin and WNT7a losses was achieved with Li ؉ , histone deacetylase inhibition, or in some cases only with combined inhibitors. Our findings provide support that E-cadherin induction by WNT͞␤-catenin signaling is an evolutionarily conserved pathway operative in lung cancer cells, and that loss of WNT7a expression may be important in lung cancer development or progression by its effects on E-cadherin.