Deregulated HOX expression, by chromosomal translocations and myeloid-lymphoid 
leukemia (MLL) rearrangements, is causal in some types of leukemia. Using 
real-time reverse transcription-PCR, we examined the expression of 43 clustered 
HOX, polycomb, MLL and FLT3 genes in 119 newly diagnosed adult acute myeloid 
leukemias (AMLs) selected from all major cytogenetic groups. Downregulated HOX 
expression was a consistent feature of favorable AMLs and, among these cases, 
inv(16) cases had a distinct expression profile. Using a 17-gene predictor in 44 
additional samples, we observed a 94.7% specificity for classifying favorable vs 
intermediate/unfavorable cytogenetic groups. Among other AMLs, HOX 
overexpression was associated with nucleophosmin (NPM) mutations and we also 
identified a phenotypically similar subset with wt-NPM. In many unfavorable and 
other intermediate cytogenetic AMLs, HOX levels resembled those in normal CD34+ 
cells, except that the homogeneity characteristic of normal samples was not 
present. We also observed that HOXA9 levels were significantly inversely 
correlated with survival and that BMI-1 was overexpressed in cases with 11q23 
rearrangements, suggesting that p19(ARF) suppression may be involved in 
MLL-associated leukemia. These results underscore the close relationship between 
HOX expression patterns and certain forms of AML and emphasize the need to 
determine whether these differences play a role in the disease process.