Keith Wheatley

hTERT expression in AML is heterogeneous and is of likely prognostic significance

Molecular events in AML (e.g. Flt3-ITD) may be exploited as nprognostic indicators or therapeutic targets. The cancer- and stem/ nprogenitor cell-related enzyme telomerase is central to maintaining nthe immortal phenotype. We investigated whether levels of ntelomerase expression are of prognostic value in AML. Following nvalidation of the assay in a range of telomerase positive and negative ncell lines and tissues, 300 samples of archived peripheral blood MNC nRNA (MRC AML12 study) were analysed blindly by Q-PCR (Light- nCycler) for hTERT (the catalytic component of telomerase). Internal nQA utilised Q-PCR for the control gene PBGD. Only samples ngenerating 4103 PBGD transcripts were analysed. Results were nexpressed as hTERT/PBGD transcripts (%) and as either hTERT npositive or negative, or high, intermediate or low (43.2%, 40.7o n3.2, o0.7, respectively, according to levels detected in normal nCD341 PBSC and PBL MNC, median of 3.2% and 0.7%, respectively) nto facilitate statistical analysis. 1169 samples were analysed, with nhTERT transcripts undetectable in 75 (hTERT range 0–255.9%, nmedian 0.17%, mean 4.3%). When analysed on an hTERT-positive or nnegative basis, there was no correlation between hTERT levels and ncytogenetic risk group, FAB subgroups, white cell count or age. nUsing multivariate regression analysis, adjusted for the known nprognostic factors (as previous, plus performance status), there was nno evidence of differences in CR rate (OR 1.14, 95%CI 0.43–3.02, np50.8), but borderline evidence of worse overall survival (OS) and ndisease-free survival (DFS) among hTERT positive patients (5 year nOS: 39% vs 53% HR 1.54 (95%CI 0.97–2.45), p50.07; 5 year DFS: 42% nvs 54% HR 1.62 (95%CI 0.96–2.74), p50.07). Classifying hTERT as nhigh, intermediate or low, 5 year OS was 34%, 50% and 47% (p50.5 nfor trend). hTERT expression in AML is heterogeneous and may be nof prognostic significance. Larger studies are required to investigate nfurther these findings.