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Research

The bone marrow microenvironment of pre-B acute lymphoblastic leukemia at single-cell resolution

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.

Research

Gain of chromosome 21 in hematological malignancies: lessons from studying leukemia in children with Down syndrome

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.

Research

Targeting cytokine- and therapy-induced PIM1 activation in preclinical models of T-cell acute lymphoblastic leukemia and lymphoma

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

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Molecular-genetic profiling and high-throughput in vitro drug screening in NUT midline carcinoma-An aggressive and fatal disease

Our data emphasize the heterogeneity of NMC and highlights genetic aberrations that could be explored to improve therapeutic strategies.

Research

Systematic chemical and molecular profiling of MLL-rearranged infant acute lymphoblastic leukemia reveals efficacy of romidepsin

Present a valuable resource for drug discovery and have identified ROM as a promising therapeutic for MLL-rearranged iALL

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Effective targeting of the P53-MDM2 axis in preclinical models of infant MLL-rearranged acute lymphoblastic leukemia.

This study describes the development and molecular characterization of a panel of patient-derived infant leukemia oncogene xenografts and their sensitivity...

Research

Reproducible Bioinformatics Analysis Workflows for Detecting IGH Gene Fusions in B-Cell Acute Lymphoblastic Leukaemia Patients

B-cell acute lymphoblastic leukaemia (B-ALL) is characterised by diverse genomic alterations, the most frequent being gene fusions detected via transcriptomic analysis (mRNA-seq). Due to its hypervariable nature, gene fusions involving the Immunoglobulin Heavy Chain (IGH) locus can be difficult to detect with standard gene fusion calling algorithms and significant computational resources and analysis times are required. We aimed to optimize a gene fusion calling workflow to achieve best-case sensitivity for IGH gene fusion detection.

Research

Pre-Clinical Evaluation of the Hypomethylating Agent Decitabine for the Treatment of T-Cell Lymphoblastic Lymphoma

T-cell lymphoblastic lymphoma (T-LBL) is a rare and aggressive lymphatic cancer, often diagnosed at a young age. Patients are treated with intensive chemotherapy, potentially followed by a hematopoietic stem cell transplantation. Although prognosis of T-LBL has improved with intensified treatment protocols, they are associated with side effects and 10-20% of patients still die from relapsed or refractory disease. Given this, the search toward less toxic anti-lymphoma therapies is ongoing.

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MYCN sensitizes neuroblastoma to the MDM2-p53 antagonists Nutlin-3 and MI-63

We hypothesized that reactivation of p53 by inhibition of its negative regulator will result in p53-mediated growth arrest and apoptosis.

Research

Silencing of TESTIN by dense biallelic promoter methylation

Aberrant promoter DNA methylation has been reported in childhood acute lymphoblastic leukaemia and has the potential to contribute to its onset and outcome