Prognostic implications of additional genomic lesions in adult Ph+ acute lymphoblastic leukemia.

Prognostic implications of additional genomic lesions in adult Ph+ acute lymphoblastic leukemia. Haematologica. 2018 Sep 06;: Authors: Fedullo AL, Messina M, Elia L, Piciocchi A, Gianfelici V, Lauretti A, Soddu S, Puzzolo MC, Minotti C, Ferrara F, Martino B, Chiusolo P, Calafiore V, Paolini S, Vignetti M, Vitale A, Guarini A, Foà R, Chiaretti S Abstract To shed light into the molecular basis of Ph+ acute lymphoblastic leukemia and to investigate the prognostic role of additional genomic lesions, we analyzed copy number aberrations using the Cytoscan HD Array in 116 newly diagnosed adult Ph+ acute lymphoblastic leukemia patients enrolled in four different GIMEMA protocols, all based on a chemotherapy-free induction strategy. This analysis showed that Ph+ acute lymphoblastic leukemia patients carry 7.8 lesions/case on average, with deletions outnumbering gains (88% vs 12%). The most common deletions were those targeting IKZF1, PAX5 and CDKN2A/B detected in 84%, 36% and 32% of cases, respectively. Patients carrying simultaneous deletions of IKZF1 plus CDKN2A/B and/or PAX5 had a significantly worse disease-free survival (24.9% vs 43.3%, p=0.026). The only IKZF1 isoform impacting on prognosis was the dominant negative (p=0.003). Copy number aberrations analysis showed that 18% of patients harbored MEF2C deletions, which were of two types, differing in size: the longer deletions were associated with the achievement of a complete molecular...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research