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

• Published in: Haematologica (Roma) Vol. 104; no. 2; pp. 312 - 318
• Main Authors: Fedullo, Anna Lucia, Messina, Monica, Elia, Loredana, Piciocchi, Alfonso, Gianfelici, Valentina, Lauretti, Alessia, Soddu, Stefano, Puzzolo, Maria Cristina, Minotti, Clara, Ferrara, Felicetto, Martino, Bruno, Chiusolo, Patrizia, Calafiore, Valeria, Paolini, Stefania, Vignetti, Marco, Vitale, Antonella, Guarini, Anna, Foà, Robin, Chiaretti, Sabina
• Format: Journal Article
• Language: English
• Published: Italy Ferrata Storti Foundation 01.02.2019
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; DNA Copy Number Variations; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Genomics - methods; Humans; Male; Middle Aged; Mutation; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - mortality; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; Prognosis; Survival Analysis; Young Adult
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.2018.196055

To 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% 12%). The most common deletions were those targeting , and , which were detected in 84%, 36% and 32% of cases, respectively. Patients carrying simultaneous deletions of plus and/or had a significantly lower disease-free survival rate (24.9% 43.3%; =0.026). The only isoform affecting prognosis was the dominant negative one ( =0.003). Analysis of copy number aberrations showed that 18% of patients harbored deletions, which were of two types, differing in size: the longer deletions were associated with the achievement of a complete molecular remission ( =0.05) and had a favorable impact on disease-free survival (64.3% 32.1% at 36 months; =0.031). These findings retained statistical significance also in multivariate analysis ( =0.057). deletions, detected in 6% of cases, were associated with the achievement of a complete molecular remission ( =0.009). These results indicate that in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia a detailed evaluation of additional deletions - including , , , and - has prognostic implications and should be incorporated in the design of more personalized treatment strategies.