Infant MLL-AF4-driven acute lymphoblastic leukemia (ALL) is a devastating disease with dismal prognosis. A lack of understanding of the unique biology of this disease, particularly its prenatal origin, has hindered improvement of survival. We perform multiple RNA sequencing experiments on fetal, neonatal, and adult hematopoietic stem and progenitor cells from human and mouse. ...

• 1. Telethon Kids Institute
• Our research
• Reports and Findings
• 2021
• October 2021

Infants with KMT2A-rearranged B-cell precursor acute lymphoblastic leukemia (ALL) have poor outcomes. There is an urgent need to identify novel agents to improve survival. Proteasome inhibition has emerged as a promising therapeutic strategy for several hematological malignancies. The aim of this study was to determine the preclinical efficacy of the selective proteasome inhibitor carfilzomib, for infants with KMT2A-rearranged ALL. ...

• 1. Telethon Kids Institute
• Our research
• Reports and Findings
• 2021
• April 2021

Infants with KMT2A-rearranged B-cell precursor acute lymphoblastic leukemia (ALL) have poor outcomes. There is an urgent need to identify novel agents to improve survival. Proteasome inhibition has emerged as a promising therapeutic strategy for several hematological malignancies. The aim of this study was to determine the preclinical efficacy of the selective proteasome inhibitor carfilzomib, for infants with KMT2A-rearranged ALL. ...

• 1. Telethon Kids Institute
• Our research
• Reports and Findings
• 2021
• April 2021

Both tumour suppressive and oncogenic functions have been reported for dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A). Herein, we performed a detailed investigation to delineate the role of DYRK1A in glioblastoma. Our phosphoproteomic and mechanistic studies show that DYRK1A induces degradation of cyclin B by phosphorylating CDC23, which is necessary for the function of the anaphase-promoting complex, a ubiquitin ligase that degrades mitotic proteins. ...

• 1. Telethon Kids Institute
• Our research
• Reports and Findings
• 2021
• April 2021

Infant acute lymphoblastic leukemia (ALL) is characterized by a high incidence of KMT2A gene rearrangements and poor outcome. We evaluated the value of minimal residual disease (MRD) in infants with KMT2A-rearranged ALL treated within the Interfant-06 protocol, which compared lymphoid-style consolidation (protocol IB) versus myeloid-style consolidation (araC, daunorubicin, etoposide/mitoxantrone, araC, etoposide). ...

• 1. Telethon Kids Institute
• Our research
• Reports and Findings
• 2021
• January 2021

The bone marrow microenvironment (BMM) plays a key role in leukemia progression, but its molecular complexity in pre-B cell acute lymphoblastic leukemia (B-ALL), the most common cancer in children, remains poorly understood. To gain further insight, we used single-cell RNA sequencing to characterize the kinetics of the murine BMM during B-ALL progression. ...

• 1. Telethon Kids Institute
• Our research
• Reports and Findings
• 2020
• November 2020

Structural and numerical alterations of chromosome 21 are extremely common in hematological malignancies. While the functional impact of chimeric transcripts from fused chromosome 21 genes such as TEL-AML1, AML1-ETO, or FUS-ERG have been extensively studied, the role of gain of chromosome 21 remains largely unknown. ...

• 1. Telethon Kids Institute
• Our research
• Reports and Findings
• 2020
• August 2020

IL7 and glucocorticoids coordinately drive aberrant activation of PIM1 and suggests that T-ALL and T-LBL patients could benefit from PIM inhibition ...

• 1. Telethon Kids Institute
• Our research
• Reports and Findings
• 2020
• May 2020

Genetic predisposition to proteome instability may be a determinant in the pathogenesis of paediatric brain cancers ...

• 1. Telethon Kids Institute
• Our research
• Reports and Findings
• 2020
• April 2020

We investigated the potential association of maternal coffee and tea consumption during pregnancy with childhood acute myeloid leukemia risk ...

• 1. Telethon Kids Institute
• Our research
• Reports and Findings
• 2019
• October 2019