Prognostic implications of additional genomic lesions in adult Philadelphia chromosome-positive acute lymphoblastic leukemia

The shed light onto the molecular basis of Philadelphia chromosome -positive 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 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia enrolled in four different GIMEMA protocols, all based on a chemotherapy-free induction strategy This analysis showed that patients with Philadelphia chromosome-positive acute lymphoblastic leukemia carry an average of 7.8 lesions/case, with deletions outnumbering gains (88% versos 12%). The most common deletions were those targeting IKZF1, PAX and CDKN2i-VB, which were detected in 84%, 36% and 32% of cases, respectively. Patients carrying simultaneous deletions of.IKZ12:1 plus CDKNZ/VB and/or PAX5 had a significantly lower disease-free survival rate (24.9% versus 43.3%; 1'=0.026). The only IKZP/ isoform affecting prognosis was the dominant negative one (P=0.003). Analysis of copy number aberrations showed that 18% of patients harbored./I1PF2C deletions, which were of two types, differing in size: the longer deletions were associated with the achievement of a complete molecular remission (P=0.05) and had a favorable impact on disease-free survival (64.3% versus 32.1% at 36 months; P=0.031). These findings retained statistical significance also in multivariate analysis (P=0.057). KRAS deletions, detected in 6% of cases, were associated with the achievement of a complete molecular remission (1'=0.009). These results indicate that in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia a detailed evaluation of additional deletions- including CDKNZA/B, PAX5, IKZF- 1, 11/IEF2C and KRAS- has prognostic implications and should be incorporated in the design of more personalized treatment strategies.