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Normal karyotype CLL show high rate of SF3B1 mutations and genomic arrays aberrations with impact on time to treatment

ABSTRACT: Chronic Lymphocytic Leukemia (CLL) is a heterogeneous disease with a variable clinical course strictly dependent on cytogenetic and molecular features. However, in 15-20% of cases both conventional cytogenetic and FISH analyses do not show any kind of abnormality. With the aim to identify dependable molecular prognostic factors in this subgroup, we evaluated 171 CLL patients, without aberrations detected by chromosome banding and FISH analysis. A comprehensive analysis was performed including genomic arrays (CGH+SNP), IGHV status, flow cytometry and a targeted sequencing. By genomic arrays, we detected 73 aberrations in 39 patients (23%). Most frequently, patients had 1 aberration (25/171; 15%), while 14 patients (8%) had at least 2 aberrations. IGHV unmutated status was present in 53/171 (31%) patients. SF3B1 was the most frequently mutated gene (26/171 patients; 15%), followed by NOTCH1 (n=15, 9%), ATM (n=5; 3%); TP53 (n=5; 3%); KLHL6 (n=5; 3%); MYD88 (n=5; 3%) and XPO1 (n=5; 3%). At univariate analysis, an adverse impact on time to treatment (TTT) was evident for SF3B1 mutations, higher white blood cell count, higher CLL cells percentage by flow cytometry, CD38 positivity, IGHV unmutated status and at least 2 genomic array abnormalities. Of them, SF3B1 mutations, CLL cells percentage, IGHV unmutated status and number of genomic array aberrations maintained their impact in multivariate analysis. In conclusion, integrating genomic and molecular data, we identified patients at higher risk for treatment need. Therefore, we suggest to evaluate these factors for a better prognostic stratification of normal karyotype CLL subset.

ORGANISM(S): Homo sapiens

PROVIDER: GSE103306 | GEO | 2017/08/31

SECONDARY ACCESSION(S): PRJNA401668

REPOSITORIES: GEO

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Normal karyotype CLL show high rate of SF3B1 mutations and genomic arrays aberrations with impact on time to treatment

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