Authors
Nicolò Peccatori, Alessia Curto, Daniela Silvestri, Stefano Rebellato, Željko Antić, Karin Nebral, Anke Katharina Bergmann, Sabine Strehl, Martin Zimmermann, Claudia Saitta, Chiara Palmi, Michela Bardini, Sanil Bhatia, Arndt Borkhardt, Manuel Quadri, Daniela Guardo, Luca Lo Nigro, Rosanna Parasole, Maria Caterina Putti, Franco Locatelli, Julia Alten, Martin Stanulla, Barbara Buldini, Jolanda Sarno, Kara L Davis, Valentino Conter, Adriana Cristina Balduzzi, Maria Grazia Valsecchi, Andrea Biondi, Andishe Attarbaschi, Martin Schrappe, Gunnar Cario, Carmelo Rizzari, Giovanni Cazzaniga, Grazia Fazio
Published in
Blood. Aug 10, 2026. Epub Aug 10, 2026.
Abstract
PAX5-altered acute lymphoblastic leukemia (PAX5-alt ALL) is a recently recognized molecular subtype of B-ALL characterized by a distinct transcriptional signature and frequent PAX5 fusions (PAX5-r). While PAX5-alt ALL has been associated with intermediate outcomes, clinical data specifically investigating pediatric PAX5-r ALL remain limited. We collected and analyzed 159 pediatric cases of PAX5-r ALL treated between 2001-2024 within AIEOP-BFM ALL studies across Italy, Germany and Austria, revealing high-risk clinical features. Comparative analyses of patients consecutively enrolled in the AIEOP-BFM ALL 2017 study (PAX5-r, n=96 vs. non-PAX5-r, n=1948) confirmed higher rates of hyperleukocytosis at diagnosis (22.9% vs. 8%, p<0.001) and enrichment of IKZF1plus profile (14.7% vs. 7.8%, p=0.0015) in PAX5-r patients. No relevant differences in terms of minimal/measurable residual disease (MRD)-based treatment response and risk-group stratification were observed. PAX5-r patients had a 4-year EFS and OS of 72.6±5.7% and 95.4±2.3%, respectively. Four-year EFS were 100%, 63.4±9.7% and 63.3±10% for standard-risk, medium-risk (MR) and high-risk (HR) groups, respectively, indicating that the poor prognostic impact of PAX5-r applies only when end-of-induction MRD is positive (MR/HR). Whole transcriptome sequencing revealed high FLT3 median expression in PAX5-r ALL and high-throughput drug screening of patient-derived xenografts (PDXs) showed marked sensitivity to several FLT3 inhibitors. Gilteritinib showed potent ex vivo cytotoxicity and synergism with dexamethasone in PAX5-r PDX models. Collectively, this study investigated clinical and biological features of pediatric PAX5-r ALL highlighting its MRD-dependent unfavorable prognosis and identifying FLT3 overexpression as a novel, potential therapeutic target.
PMID:
42574325
Bibliographic data and abstract were imported from PubMed on 11 Aug 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 5
- Comments 0