767 research outputs found

    NON-CODING NOTCH1 MUTATIONS IN CHRONIC LYMPHOCYTIC LEUKEMIA; THEIR CLINICAL IMPACT IN THE UK CLL4 TRIAL

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    Multi-label classification using ensembles of pruned sets

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    This paper presents a Pruned Sets method (PS) for multi-label classification. It is centred on the concept of treating sets of labels as single labels. This allows the classification process to inherently take into account correlations between labels. By pruning these sets, PS focuses only on the most important correlations, which reduces complexity and improves accuracy. By combining pruned sets in an ensemble scheme (EPS), new label sets can be formed to adapt to irregular or complex data. The results from experimental evaluation on a variety of multi-label datasets show that [E]PS can achieve better performance and train much faster than other multi-label methods

    The morphology of CLL revisited: the clinical significance of prolymphocytes and correlations with prognostic/molecular markers in the LRF CLL4 trial.

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    Historically, an increase in the percentage and number of circulating prolymphocytes in chronic lymphocytic leukaemia (CLL) has been associated with strong expression of surface immunoglobulin, trisomy 12 and a poor outcome. This study re-examines the biological and clinical significance of increased peripheral blood prolymphocytes in 508 patients at entry into the randomized UK Leukaemia Research Fund CLL4 trial. It also investigates the associations between increased prolymphocytes and a comprehensive array of biomarkers. 270 patients (53%) had <5% prolymphocytes, 167 (33%) had 5-9%, 60 (12%) had 10-14% and 11 (2%) had ā‰„15% prolymphocytes. We show that a higher proportion of prolymphocytes (ā‰„10%) was independently associated with NOTCH1 mutations (PĀ =Ā 0Ā·006), absence of 13q deletion (PĀ =Ā 0Ā·001), high CD38 expression (PĀ =Ā 0Ā·02) and unmutated IGHV genes (PĀ =Ā 0Ā·01). Deaths due to Richter syndrome were significantly more common amongst patients who had ā‰„10% vs <10% prolymphocytes (13% vs 2%) respectively (PĀ <Ā 0Ā·0001). ā‰„10% prolymphocytes was also associated with a shorter progression-free survival (Hazard ratio [HR] 1Ā·50 [95% confidence interval [CI]: 1Ā·16-1Ā·93], PĀ =Ā 0Ā·002) and overall survival (HR 1Ā·99 [95% CI: 1Ā·53-2Ā·59], PĀ <Ā 0Ā·0001). Our data support the routine examination of blood films in CLL and suggest that a finding of an increased proportion of prolymphocytes may be a trigger for further evaluation of clinical and laboratory features of progressive disease
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