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Defining the prognosis of individual cancer sufferers remains a significant clinical challenge. Here we assessed the ability of high-resolution single telomere length analysis ( STELA), combined with an experimentally derived definition of telomere dysfunction, to predict the clinical outcome of patients with chronic lymphocytic leukaemia ( CLL). We defined the upper telomere length threshold at which telomere fusions occur and then used the mean of the telomere 'fusogenic' range as a prognostic tool. Patients with telomeres within the fusogenic range had a significantly shorter overall survival ( P < 0·0001; Hazard ratio [ HR] = 13·2, 95% confidence interval [ CI] = 11·6-106·4) and this was preserved in early-stage disease patients ( P < 0·0001, HR=19·3, 95% CI = 17·8-802·5). Indeed, our assay allowed the accurate stratification of Binet stage A patients into those with indolent disease (91% survival at 10 years) and those with poor prognosis (13% survival at 10 years). Furthermore, patients with telomeres above the fusogenic mean showed superior prognosis regardless of their IGHV mutation status or cytogenetic risk group. In keeping with this finding, telomere dysfunction was the dominant variable in multivariate analysis. Taken together, this study provides compelling evidence for the use of high-resolution telomere length analysis coupled with a definition of telomere dysfunction in the prognostic assessment of CLL. [ABSTRACT FROM AUTHOR]

Defining the prognosis of individual cancer sufferers remains a significant clinical challenge. Here we assessed the ability of high‐resolution single telomere length analysis (STELA), combined with an experimentally derived definition of telomere dysfunction, to predict the clinical outcome of patients with chronic lymphocytic leukaemia (CLL). We defined the upper telomere length threshold at which telomere fusions occur and then used the mean of the telomere ‘fusogenic’ range as a prognostic tool. Patients with telomeres within the fusogenic range had a significantly shorter overall survival (P < 0·0001; Hazard ratio [HR] = 13·2, 95% confidence interval [CI] = 11·6–106·4) and this was preserved in early‐stage disease patients (P < 0·0001, HR=19·3, 95% CI = 17·8–802·5). Indeed, our assay allowed the accurate stratification of Binet stage A patients into those with indolent disease (91% survival at 10 years) and those with poor prognosis (13% survival at 10 years). Furthermore, patients with telomeres above the fusogenic mean showed superior prognosis regardless of their IGHV mutation status or cytogenetic risk group. In keeping with this finding, telomere dysfunction was the dominant variable in multivariate analysis. Taken together, this study provides compelling evidence for the use of high‐resolution telomere length analysis coupled with a definition of telomere dysfunction in the prognostic assessment of CLL. [ABSTRACT FROM AUTHOR]

Background. Heat shock protein 72 (Hsp72) is a highly inducible stress protein and molecular chaperone. Cancers have been shown to be associated with increased Hsp72 expression within the tumour itself and this may lead to resistance to apoptosis. Methods. Peripheral blood mononuclear cells (PBMC) were isolated from patients diagnosed with chronic lymphocytic leukaemia (CLL) ( n = 27) and chronic myelomonocytic leukaemia (CMML) ( n = 16) and Hsp72 expression was characterized on both the cell surface and intracellularly by flow cytometry. To allow for comparison PBMC from breast cancer patients ( n = 25) and healthy volunteers ( n = 19) were included. Results. Both lymphocytes and monocytes from CLL and CMML patients showed high levels of total Hsp72 expression (4-6 fold increase) in comparison to breast cancer and healthy subjects. The majority of Hsp72 in these tumours was determined to be cell-surface expressed (64-93% of cell total Hsp72). Conclusions. A correlation was observed between lymphocyte and monocyte total Hsp72 expression ( p < 0.001) suggesting a common stress response pathway may exist in these blood cells and there are stress conditions present within the circulation. Hsp72 expression was not found to be related to white blood cell count. [ABSTRACT FROM AUTHOR]