Telomere length predicts progression and overall survival in chronic lymphocytic leukemia: data from the UK LRF CLL4 trial

elomere erosion and fusion have an important role in the pathology of many common human malignancies including chronic lymphocytic leukemia (CLL).1, 2 Previous studies in CLL have shown that short telomeres defined on the basis of the median value or receiver operating characteristic analysis are associated with unmutated IGHV genes, poor-risk genomic abnormalities, genomic complexity and high expression of CD38, CD49d and ZAP70 whereas long telomeres are associated with increasing IGHV mutational load, isolated deletion of 13q and low CD49d expression. In addition, in predominantly diagnostic or mixed patient cohorts, telomere length (TL) predicts time to first treatment and/or overall survival (OS) in multivariate analyses of models incorporating established biomarkers.3, 4, 5, 6, 7 However uncertainties about the most clinically relevant measure of TL, the optimal choice of assay, the need for assay standardisation and the lack of published data on the prognostic value of TL in patients entered into randomised trials have hindered the implementation of TL measurement into routine clinical practice. We have attempted to address these issues by measuring TL using monochrome multiplex Q-PCR (MMQ-PCR) in 384 patients at randomisation into the UK LRF CLL4 phase 3 chemotherapy trial (Supplementary Table S1), of whom 111 samples were also screened by single telomere length analysis (STELA). TL and established biomarkers were measured as previously describe