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Challenges posed by COVID-19 to children with cancerDevelopment of standardised guidance by national and regional authorities for reducing the risk of SARS-CoV-2 transmission to children with cancer
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Therapeutic targeting of the leukaemia microenvironmentIn recent decades, the conduct of uniform prospective clinical trials has led to improved remission rates and survival for patients with acute myeloid leukaemia and acute lymphoblastic leukaemia. However, high-risk patients continue to have inferior outcomes, where chemoresistance and relapse are common due to the survival mechanisms utilised by leukaemic cells.
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Bioenergetic modulation overcomes glucocorticoid resistance in T-lineage acute lymphoblastic leukaemiaDrug-resistant forms of acute lymphoblastic leukaemia (ALL) are a leading cause of death from disease in children.
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Hypomethylation of the CTGF gene locus is a common feature of paediatric pre-B acute lymphoblastic leukaemiaWe identified consistent hypomethylation of the CTGF locus in primary pre-B ALL specimens regardless of CTGF expression.
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Validation of a mouse xenograft model system for gene expression analysis of human acute lymphoblastic leukaemiaPre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms.
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Immunogenicity of the inactivated influenza vaccine in children who have undergone allogeneic haematopoietic stem cell transplantThis study provides evidence to support annual inactivated influenza vaccine administration to children following allogeneic haematopoietic stem cell transplant
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Invasive fungal disease and antifungal prophylaxis in children with acute leukaemia: a multicentre retrospective Australian cohort studyInvasive fungal disease (IFD) is a common and important complication in children with acute myeloid leukaemia (AML). We describe the epidemiology of IFD in a large multicentre cohort of children with AML.
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KMT2A-rearranged acute lymphoblastic leukaemiaKMT2A-rearranged acute lymphoblastic leukaemia (ALL) represents a high risk subtype of childhood ALL. Historical treatment strategies have comprised of intensification with conventional chemotherapy. However, outcomes have remained consistently poor compared to the advances that have been seen for other ALL subtypes, particularly for infants diagnosed before their first birthday
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RUNX2 regulates leukemic cell metabolism and chemotaxis in high-risk T cell acute lymphoblastic leukemiaT cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with inferior outcome compared with that of B cell ALL. Here, we show that Runt-related transcription factor 2 (RUNX2) was upregulated in high-risk T-ALL with KMT2A rearrangements (KMT2A-R) or an immature immunophenotype. In KMT2A-R cells, we identified RUNX2 as a direct target of the KMT2A chimeras, where it reciprocally bound the KMT2A promoter, establishing a regulatory feed-forward mechanism.
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Outcomes for Australian children with relapsed/refractory acute lymphoblastic leukaemia treated with blinatumomabWe report on the Australian experience of blinatumomab for treatment of 24 children with relapsed/refractory precursor B-cell acute lymphoblastic leukaemia (B-ALL) and high-risk genetics, resulting in a minimal residual disease (MRD) response rate of 58%, 2-year progression-free survival (PFS) of 39% and 2-year overall survival of 63%. In total, 83% (n = 20/24) proceeded to haematopoietic stem cell transplant, directly after blinatumomab (n = 12) or following additional salvage therapy (n = 8).