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. 2019 Feb;33(2):518-558.
doi: 10.1038/s41375-018-0255-1. Epub 2018 Sep 12.

CLL Cells Cumulate Genetic Aberrations Prior to the First Therapy Even in Outwardly Inactive Disease Phase

Free PMC article

CLL Cells Cumulate Genetic Aberrations Prior to the First Therapy Even in Outwardly Inactive Disease Phase

María Hernández-Sánchez et al. Leukemia. .
Free PMC article

Conflict of interest statement

The authors declare that they have no conflict of interest.


Fig. 1
Fig. 1
Sampling points and follow-ups of the tested cohort. Time-point 1 (TP1) for all tested samples was set to the inactive stage of the disease close to the diagnosis (median from diagnosis to TP1 = 2.1 months). Second time-points (TP2) were all collected prior to CLL-related therapy. Three groups of patients were then characterized based on disease activity in the TP2: (i) Active disease (AD) group - patients with TP2 in disease’s active phase (n = 20, median TTP = 33.9 months, median TTFT = 41.9 months); (ii) Stable disease (SD) group - patients with TP2 in disease’s inactive phase followed by active phase and therapy need (n = 6, median of time to progression (TTP) = 44.7 months, median of time to first treatment (TTFT) = 46.8 months); (iii) Indolent disease (ID) group - patients with TP2 taken in inactive phase, no disease activity or therapy need was reached during follow-up of 3 years (n = 9, median follow-up = 158.1 months). Only one ID case (P31) progressed after 150 months and required therapy intervention
Fig. 2
Fig. 2
List of genes with driver mutations validated using deep targeted sequencing and their changes in variant allele frequency between time-points. Cut-off 5% of VAF was applied for validation of identified mutations. Allele frequency differences were tested across leukemia samples using a Fisher’s exact test. Mutations were considered to be changed if they were significantly different between samples (evolution p-value < 0.05) and their ratio of VAF between TP2 and TP1 was higher than 1.5 (for “increased” mutations) or lower than 0.375 (for “decreased” mutations). Genes with dark blue labels (on the left axis) were CLL drivers previously identified in Puente et al.2 and Landau et al.3 and, where those in light blue were unknown as CLL drivers to date

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