Prognostic significance of the percentage of 13q14 deletion in Argentinean patients with chronic lymphocytic leukemia. International

VIRGINIA PALAU NAGORE; FLAVIA STELLA; ANDREA KRZYWINSKI; EVANGELINA AGRIELLO; VIVIANA HELLER; MIGUEL A PAVLOVSKY; ISABEL GIERE; CAMILA GALVANO; LORENA ZANELLA; CECILIA RODRÍGUEZ; CAROLINA PAVLOVSKY; BELÉN BRIZUELA; CARMEN STANGANELLI; CECILIA LANG; RAIMUNDO BEZARES; ISABEL GIERE; IRMA SLAVUTSKY

Edinburgh

Workshop; International Workshop on Chronic Lymphocytic Leukemia (iwCLL); 2019

International Workshop on Chronic lymphocytic leukemia

Deletion 13q14 (del13q14) on fluorescence in situ hybridization (FISH) analysis is the most common cytogenetic abnormality in chronic lymphocytic leukemia (CLL), and is a favorable prognostic biomarker when detected as a sole abnormality. However, patients with isolated del13q14 are a heterogeneous group, with a different outcome depending on the number of cells displaying this aberration. Specifically, more aggressive clinical courses were documented for isolated del13q14 CLL patients carrying high percentages of 13q14 deleted nuclei. In clinical practice, to separate del13q14 cases into subsets with different outcomes, cut-off values ranging between 60% and 85% have been proposed. In this study, we evaluated the percentage of leukemic cells with isolated del13q14 in Argentinean CLL patients in order to identify subsets with a different progression risk as well as to provide a reference cut-off value for clinical practice in our country.A total of 101 CLL cases with isolated del13q14 (58 males and 43 females; mean age: 61 years, range: 36-83 years; Rai stages: 0: 42.5%, I-II: 42.5%, III-IV: 15%) were analyzed. The study was approved by the local Ethics Committee. All individuals provided their informed written consent. Chromosome analysis was performed on stimulated peripheral blood lymphocytes cultures. FISH study was performed using the CLL panel according to manufacturer´s protocol (Live-Lexel, Argentina). Two hundred interphase nuclei were analyzed for each probe. The cut-offs for positive values (mean of normal control + 3 standard deviations) determined from ten cytogenetically normal donors were as follows: 3%, 10%, 7.5%, and 5.5% for trisomy 12, monosomies of D13S319, ATM, and TP53, respectively. IGHV (immunoglobulin heavy chain variable region) mutational status was analyzed by RT-PCR and bi-directional sequencing as previously described (Clin Lymphoma Myeloma Leuk 2013; 13:447-57). IGHV sequences with