NOTCH1, SF3B1, BIRC3 AND TP53 mutations in chronic lymphocytic leukemia patients undergoing first-line treatment: correlation with biological parameters and response to treatment

Abstract In chronic lymphocytic leukemia NOTCH1, SF3B1, BIRC3 and TP53 disruptions are recurrent and affect survival. To define their incidence and clinical impact in patients undergoing first-line treatment, we evaluated 163 cases enrolled in the GIMEMA LLC0405 protocol (fludarabine plus alemtuzumab or fludarabine plus cyclophosphamide), for young patients, or in the ML21445 protocol (chlorambucil plus rituximab), for elderly. NOTCH1, SF3B1, BIRC3 and TP53 disruptions were detected in 15.9\%, 12.2\%, 8.6\% and 10.4\% of cases. NOTCH1 mutations correlated with a shorter treatment-free interval (p=0.058), an unmutated immunoglobulin heavy variable genes (IGHV) status (p<0.0001), CD38 and ZAP-70 expression (p=0.0025 and 0.026, respectively) and trisomy 12 (p=0.0028), SF3B1 mutations with an unmutated IGHV status (p=0.02), and BIRC3 disruptions with an unmutated IGHV configuration (p=0.01) and 11q deletion (p