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Aging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic leukemiaCancer cells display DNA hypermethylation at specific CpG islands in comparison to their normal healthy counterparts, but the mechanism that drives this so-called CpG island methylator phenotype (CIMP) remains poorly understood. Here, we show that CpG island methylation in human T-cell acute lymphoblastic leukemia (T-ALL) mainly occurs at promoters of Polycomb Repressor Complex 2 (PRC2) target genes that are not expressed in normal or malignant T-cells and which display a reciprocal association with H3K27me3 binding.
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An Anti-VEGF-B Antibody Reduces Abnormal Tumor Vasculature and Enhances the Effects of ChemotherapyThe vascular endothelial growth factors and their receptors are key regulators of blood vessel formation, including in tumors, where their deregulated function can promote the production of aberrant, leaky blood vessels, supporting tumor development.
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Childhood Cancer Incidence and Survival in South Australia and the Northern Territory, 1990–2017, with Emphasis on Indigenous PeoplesReports of a rise in childhood cancer incidence in Australia and globally prompted the investigation of cancer incidence and survival in South Australia and the Northern Territory over a 28-year period, with emphasis on Indigenous peoples.
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Insights into the Clinical, Biological and Therapeutic Impact of Copy Number Alteration in CancerCopy number alterations (CNAs), resulting from the gain or loss of genetic material from as little as 50 base pairs or as big as entire chromosome(s), have been associated with many congenital diseases, de novo syndromes and cancer. It is established that CNAs disturb the dosage of genomic regions including enhancers/promoters, long non-coding RNA and gene(s) among others, ultimately leading to an altered balance of key cellular functions.
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The bone marrow microenvironment of pre-B acute lymphoblastic leukemia at single-cell resolutionThe bone marrow microenvironment 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.
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Tumour draining lymph node-generated CD8 T cells play a role in controlling lung metastases after a primary tumour is removed but not when adjuvant immunotherapy is usedSurgical resection of cancer remains the frontline therapy for millions of patients annually, but post-operative recurrence is common, with a relapse rate of around 45% for non-small cell lung cancer. The tumour draining lymph nodes (dLN) are resected at the time of surgery for staging purposes, and this cannot be a null event for patient survival and future response to immune checkpoint blockade treatment. This project investigates cancer surgery, lymphadenectomy, onset of metastatic disease, and response to immunotherapy in a novel model that closely reflects the clinical setting. In a murine metastatic lung cancer model, primary subcutaneous tumours were resected with associated dLNs remaining intact, completely resected or partially resected.
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Clinical phenotypes and prognostic features of embryonal tumours with multi-layered rosettes: a Rare Brain Tumor Registry studyEmbryonal tumours with multi-layered rosettes (ETMRs) are a newly recognised, rare paediatric brain tumour with alterations of the C19MC microRNA locus. Due to varied diagnostic practices and scarce clinical data, disease features and determinants of outcomes for these tumours are poorly defined. We did an integrated clinicopathological and molecular analysis of primary ETMRs to define clinical phenotypes, and to identify prognostic factors of survival and key treatment modalities for this orphan disease.
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Parents' Experiences of Childhood Cancer During the COVID-19 Pandemic: An Australian PerspectiveCOVID-19 has had far-reaching impacts including changes in work, travel, social structures, education, and healthcare. This study aimed to explore the experiences of parents of children receiving treatment for cancer during the COVID-19 pandemic.
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Down syndrome-associated leukaemias: current evidence and challengesChildren with Down syndrome (DS) are at increased risk of developing haematological malignancies, in particular acute megakaryoblastic leukaemia and acute lymphoblastic leukaemia. The microenvironment established by abnormal haematopoiesis driven by trisomy 21 is compounded by additional genetic and epigenetic changes that can drive leukaemogenesis in patients with DS.
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COVID-19 vaccination in children and adolescents aged 5 years and older undergoing treatment for cancer and non-malignant haematological conditions: Australian and New Zealand Children’s Haematology/Oncology Group consensus statementThe Australian Technical Advisory Group on Immunisation and New Zealand Ministry of Health recommend all children aged ≥ 5 years receive either of the two mRNA COVID-19 vaccines: Comirnaty (Pfizer), available in both Australia and New Zealand, or Spikevax (Moderna), available in Australia only. Both vaccines are efficacious and safe in the general population, including children. Children and adolescents undergoing treatment for cancer and immunosuppressive therapy for non-malignant haematological conditions are particularly vulnerable, with an increased risk of severe or fatal COVID-19.