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<0.0001) NOTCH1 and SF3B1 did not appear to impact on overall response, while an inferior response was observed for BIRC3- and TP53-disrupted cases in the LLC0405 and ML21445 protocol, respectively. Progression-free survival, evaluable in the LLC0405 protocol - not affected by NOTCH1, SF3B1 and TP53 - appeared inferior for BIRC3 disruption. NOTCH1 and SF3B1 mutations may be overcome by aggressive regimens, while BIRC3 might impact on outcome also in intensive regimens.

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

ROSSI, Davide;GAIDANO, Gianluca;
2014-01-01

Abstract

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<0.0001) NOTCH1 and SF3B1 did not appear to impact on overall response, while an inferior response was observed for BIRC3- and TP53-disrupted cases in the LLC0405 and ML21445 protocol, respectively. Progression-free survival, evaluable in the LLC0405 protocol - not affected by NOTCH1, SF3B1 and TP53 - appeared inferior for BIRC3 disruption. NOTCH1 and SF3B1 mutations may be overcome by aggressive regimens, while BIRC3 might impact on outcome also in intensive regimens.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11579/42358
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