Association between micronucleus formation and genomic complexity in patients with chronic lymphocytic leukemia

PALMITELLI M; KRZYWINSKI A; SLAVUTSKY I; STELLA F; GONZÁLEZ CID M; STANGANELLI C; BEZARES R

Buenos Aires

Congreso; 3er Congreso Iberoamericano de Leucemia Linfocítica Crónica; 2018

Sociedad Argentina de Hematología

Genomic instability is a hallmark of human cancers, promoting oncogenesis and clonal evolution. Basal chromosome instability measured by micronucleus (MN) frequency was evaluated in 74 patients with chronic lymphocytic leukemia (CLL) and 15 normal controls (NC). Cytogenetic, FISH and IGHV mutational status analysis were performed. The study was approved by the local Ethics Committee. All patients provided their written informed consent. An increased MN frequency in patients (3.1 ± 1.7%) compared to NC (0.7 ± 0.3%) (p = 0.0001) was observed. No difference between cases with normal (2.94 ± 1.83%) and abnormal karyotypes (3.08 ± 1.5%) was found. Considering FISH risk groups, the highest MN frequency was detected in patients with ≥ 2 FISH alterations (3.71 ± 1.87%) followed by cases with del13q14 (2.78 ± 1.83%), trisomy 12 (2.79 ± 1.7%), and no alterations (NA) (2.39±1.14%), with differences between ≥ 2 FISH alterations and NA groups (p=0.018). When the cohort was divided using the cut-off obtained by ROC analysis (2.2%), a higher MN frequency in patients with ≥ 2 FISH alterations compared to the other FISH groups (p = 0.04) was found. Interestingly, cases with high MN frequency had shorter time to first treatment than those with low frequency (p = 0.011). No differences between cases with mutated and unmutated IGHV status were observed. Our results support the strong association between MN formation and genomic complexity as well as their influence on poor outcome in this pathology.