Quantitative HOX expression in chromosomally defined subsets of acute myelogenous leukemia

Abstract

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.

Leukaemic transformation by CALM–AF10 involves upregulation of Hoxa5 by hDOT1L

“…cDNA microarray studies have revealed that overexpression of late Hoxa genes and Bmi-1 are a characteristic of leukaemias involving CALM-AF10 and some MLL-fusion proteins [12][13][14] . In particular, over-expression of Hoxa9 has been demonstrated to be crucial for leukaemias involving MLL-ENL and MLL-AF10 fusion proteins 5,15,16 .…”

Hox genes in hematopoiesis and leukemogenesis

“…The unequivocal role of Hox genes in the pathogenesis of acute leukemia A central role for HOX genes in hematological malignancies is supported by the frequently observed elevation of HOX and MEIS1 gene expression in AML patient samples (Golub et al, 1999;Kawagoe et al, 1999;Lawrence et al, 1999;Afonja et al, 2000;Drabkin et al, 2002). Indeed, HOXA9 is the single most highly correlated gene (out of 6817) for poor prognosis in AML (Golub et al, 1999).…”

The proteasome inhibitor PS-341 overcomes TRAIL resistance in Bax and caspase 9-negative or Bcl-xL overexpressing cells

“…Quantitative RT-PCR assays were performed using the ABI 5700 real-time system with SYBR-green fluorescence, as described in detail (Drabkin et al, 2002). Briefly, cDNA was synthesized from 2.5 mg of total RNA isolated by the method of Chomczynski and Sacchi (1987) with Superscript II (Invitrogen Life Technologies, Carlsbad, CA, USA) using random primers and conditions recommended by the manufacturer.…”