Association between genomic rearrangements and instability in patients with chronic lymphocytic leukemia.

FLAVIA STELLA; MARCELA GOZÁLEZ CID; MICAELA PALMITELLI; IRMA SLAVUTSKY; ANDREA KRZYWINSKI

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Sociedad Argentina de Investigación Clínica

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with a highly variable clinical course. Genomic instability (GI), evidenced by acquired genetic aberrations, has an important role in CLL pathogenesis, as the number of genomic alterations was shown to increase throughout the course from newly diagnosed to progressive and further to relapsed CLL. GI can be assessed by means of chromosome aberrations (CA) and micronucleus (MN) analysis. Cytogenetic and FISH (fluorescence in situ hybridization) studies are important prognostic factors in CLL. We have analyzed GI in 81 untreated CLL patients (41 males; mean age: 65.6 years; range: 42-83 years) and 6 normal controls. Cytogenetic analysis was performed on stimulated peripheral blood lymphocyte cultures. FISH was performed using the CLL panel according to manufacturer?s protocol. For each patient, CA was evaluated on 50 metaphases while 250 interphase nuclei were analyzed for MN frequency. An increased number of CAs in CLL patients compared to controls (6.89±5.4% vs 0.25±0.4%, p=0.004), with the higher value in cases with abnormal (8.54±5.8%) vs normal (5.2±4.5%) karyotype (p=0.008), was observed. Considering FISH risk groups, the analysis showed a higher frequency of CA in patients with deletions 11q22/17p13 (8.4±5.6%) associated to poor prognosis than those with no alterations or deletion 13q14 (5.1±3.8%) (p=0.012) related to a better outcome, and +12 (3.6±2.3%) with intermediate risk (p=0.010). MN analysis displayed an increased frequency in CLL patients (3.1±1.7%) compared to controls (0.7±0.3%) (p=0.001) but no significant differences between cytogenetic or FISH groups were observed. Our results show the presence of basal genomic instability in untreated CLL patients as measured by both CA and MN techniques, as well as an association with cytogenetic and FISH risk groups, being to our knowledge the first study taking into account these prognostic factors.