We investigated at two time points a longitudinal cohort of 27 untreated Chronic Lymphocytic Leukemia (CLL) patients with either stable or progressive disease. The sequenced genes included BCOR, EGR2, HIST1H1E, ITPKB, KRAS, MED12, NRAS, RIPK1, SAMHD1, ATM, BIRC3, BRAF, CHD2, DDX3X, DDX3Y, FBXW7, KIT, KLHL6, MAPK1, MYD88, NOTCH1, PIK3CA, POT1, SF3B1, TP53, XPO1 and ZMYM3, which were previously identified as mutated in CLL studies.. Genetic dynamics in untreated chronic lymphocytic leukemia patients with either stable or progressive disease: a longitudinal study.

Clonal evolution of Chronic Lymphocytic Leukemia (CLL) often follows chemotherapy and is associated with adverse clinical outcome. We investigated whether selection and expansion of CLL clone(s) is a pre-requisite for the aggressive disease shift in untreated CLLs. To this end, we investigated at two time points a longitudinal cohort of 49 untreated CLL patients with either stable or progressive disease. We studied whole genome copy number variation, CLL-associated chromosomal aberrations and mutations in 27 CLL-related genes. Untreated patients undergoing CLL progression exhibited clonal evolution. The genetic abnormalities changed over time in both sets of patients but the patients with progressive CLL acquired or lost clones faster than the patients with stable disease. Moreover, compared to the patients with stable disease, those with progressive CLL showed differences in quantity and frequency of nucleotide variations changed over-time, suggesting that a high genetic dynamic may represent an early indicator of poor clinical outcome.