¹Division of Medical Oncology, University of Colorado Health Sciences and Cancer Centers, Denver, CO, USA

²Department of Biostatistics, University of Colorado Health Sciences and Cancer Centers, Denver, CO, USA

³IBMIG, CNRS FRE 2224, Université de Poitiers, Poitiers, France

⁴Département d'Hématologie et Oncologie Medicale, CHU de Poitiers, Poitiers, France

⁵The Children's Hospital and University of Colorado Cancer Center, Denver, CO, USA

⁶Laboratoire d'Hématologie, CHU de Poitiers, CNRS FRE 2224, Poitiers, France

Correspondence to: H A Drabkin, Division of Medical Oncology, Box B-171 University of Colorado Health Sciences Center, 4200 E 9th Ave, Denver, CO 80262, USA; Fax: 303-315-8825

^aPresent address: University of Florida, Department of Pediatric Hematology/Oncology, Gainesville, FL 32610-0296, USA

We used a degenerate RT-PCR screen and subsequent real-time 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 inter-related. 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.

Leukemia (2002) 16, 186-195. DOI: 10.1038/sj/leu/2402354

homeodomain; TALE; MLL; chromosome translocation; AML