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Global phosphoproteomics reveals DYRK1A regulates CDK1 activity in glioblastoma cellsBoth 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.
Research
Acute Leukaemia of Ambiguous Lineage Presenting as a Focal Bone Lesion: a Case ReportAcute leukaemia is the most common childhood malignancy. Almost all cases are classified as acute lymphoblastic leukaemia or acute myeloid leukaemia. Acute leukaemia of ambiguous lineage (ALAL) is a rare form of acute leukaemia that cannot be classified by a single lineage. Like other acute leukaemias, ALAL typically presents with nonspecific symptoms such as fatigue, fever, or bleeding.
Research
Defining the fetal origin of MLL-AF4 infant leukemia highlights specific fatty acid requirementsInfant 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.
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The bone marrow microenvironment of pre-B acute lymphoblastic leukemia at single-cell resolutionThe 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 syndromeStructural 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.
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Clinical Implications of Minimal Residual Disease Detection in Infants With KMT2A-Rearranged Acute Lymphoblastic Leukemia Treated on the Interfant-06 ProtocolInfant 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).
Research
Preclinical efficacy of azacitidine and venetoclax for infant KMT2A-rearranged acute lymphoblastic leukemia reveals a new therapeutic strategyInfants with KMT2A-rearranged B-cell acute lymphoblastic leukemia (ALL) have a dismal prognosis. Survival outcomes have remained static in recent decades despite treatment intensification and novel therapies are urgently required.
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Reproducible Bioinformatics Analysis Workflows for Detecting IGH Gene Fusions in B-Cell Acute Lymphoblastic Leukaemia PatientsB-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
The relationship between medication literacy and skin adverse reactions in non-small-cell lung cancer patients undergoing targeted EGFR-The KidstherapyHigh medication literacy is the basis of rational medication application and is essential for the management of severe adverse drug reactions. The objective of the present study was to assess the level of medication literacy and determine the association between medication literacy and skin adverse drug reactions in non-small-cell lung cancer (NSCLC) patients undergoing targeted epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-The Kids) therapy.
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A biobank of pediatric patient-derived-xenograft models in cancer precision medicine trial MAPPYACTS for relapsed and refractory tumorsPediatric patients with recurrent and refractory cancers are in most need for new treatments. This study developed patient-derived-xenograft (PDX) models within the European MAPPYACTS cancer precision medicine trial.