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A New Era for PPARγ: Covalent Ligands and Therapeutic Applications

Peroxisome proliferator-activated receptor γ (PPARγ) is a prominent ligand-inducible transcription factor involved in adipocyte differentiation, glucose homeostasis, insulin sensitivity, inflammation, and cell proliferation, making it a therapeutic target for diabetes, metabolic syndrome, autoimmune diseases, and cancer. 

Beyond bone: the emerging role of osteoclasts in immune regulation, leukemia development and following myeloablative therapy

Osteoclasts are important regulators of bone remodeling, with an established role in maintaining skeletal homeostasis. The emergence of osteoimmunology has identified osteoclasts as key players in the immune system. In particular, osteoclasts can initiate bi-directional crosstalk mechanisms with hematopoietic stem cells and various immune cells, such as T cells, B cells and NK cells, to influence hematopoiesis and inflammatory response.

Histone methyltransferase PRDM9 promotes survival of drug-tolerant persister cells in glioblastoma

Chemotherapy often kills a large fraction of cancer cells but leaves behind a small population of drug-tolerant persister cells. These persister cells survive drug treatments through reversible, non-genetic mechanisms and cause tumour recurrence upon cessation of therapy. Here, we report a drug tolerance mechanism regulated by the germ-cell-specific H3K4 methyltransferase PRDM9. 

Editorial: Bench to bedside: translating pre-clinical research into clinical trials for childhood brain tumors

Nick Raelene Gottardo Endersby MBChB FRACP PhD BSc (Hons) PhD Head of Paediatric and Adolescent Oncology and Haematology, Perth Children’s Hospital;

Leukaemia

Leukaemia, also spelled leukemia, is a cancer that develops in the bone marrow and results in abnormal white blood cells. It is the most common cancer in children, accounting for almost a third of all childhood & teen cancers.

Biologic and Clinical Analysis of Childhood Gamma Delta T-ALL Identifies LMO2/STAG2 Rearrangements as Extremely High Risk

Acute lymphoblastic leukemia expressing the gamma delta T-cell receptor (γδ T-ALL) is a poorly understood disease. We studied 200 children with γδ T-ALL from 13 clinical study groups to understand the clinical and genetic features of this disease. We found age and genetic drivers were significantly associated with outcome.

Invasive fungal disease and antifungal prophylaxis in children with acute leukaemia: a multicentre retrospective Australian cohort study

Invasive fungal disease 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.

Local therapy with combination TLR agonists stimulates systemic anti-tumor immunity and sensitizes tumors to immune checkpoint blockade

W. Joost Ben Lizeth Rachael Tao Omar Lesterhuis Wylie Orozco Morales Zemek Wang Elaskalani BSc PhD BSc, MSc, PhD BSc (Hons), PhD PhD BSc, MSc, PhD

In their own words: advice from parents of children with cancer

Approximately 770 children are diagnosed with cancer in Australia every year. Research has explored their experiences and developed recommendations for improving support provided to families. These have included the provision of psychology services, improved communication between healthcare professionals and parents, and increased information for families. 

Disruption of cotranscriptional splicing suggests that RBM39 is a therapeutic target in acute lymphoblastic leukemia

There are few options for patients with relapse/refractory B-cell acute lymphoblastic leukemia, thus this is a major area of unmet medical need. Here, we reveal that inclusion of a poison exon in RBM39, which could be induced both by CDK9 or CDK9 independent CMGC (cyclin-dependent kinases, mitogen-activated protein kinases, glycogen synthase kinases, CDC-like kinases) kinase inhibition, is recognized by the nonsense-mediated mRNA decay pathway for degradation.