Clinical impact of small TP53 mutated subclones in chronic lymphocytic leukemia

摘要: TP53 mutations are strong predictors of poor survival and refractoriness in chronic lymphocytic leukemia (CLL) have direct implications for disease management. Clinical information on is limited to lesions represented >20% leukemic cells. Here, we tested the clinical impact prediction chemorefractoriness very small mutated subclones. The gene underwent ultra-deep-next generation sequencing (NGS) 309 newly diagnosed CLL. A robust bioinformatic algorithm was established highly sensitive detection few cells (down 3 out ∼1000 wild-type cells). Minor subclones were validated by independent approaches. Ultra-deep-NGS identified 28/309 (9%) untreated CLL that, due their low abundance (median allele frequency: 2.1%), missed Sanger sequencing. Patients harboring showed same phenotype (hazard ratio = 2.01; P .0250) as those patients carrying clonal lesions. By longitudinal analysis, before treatment became predominant population at time relapse anticipated development chemorefractoriness. This study provides a proof-of-principle that minor detected diagnosis an important driver subsequent course.