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PEGasparaginase is known to be a critical drug for treating pediatric acute lymphoblastic leukemia (ALL), however, there is insufficient evidence to determine the optimal dose for infants who are less than one year of age at diagnosis. This international study was conducted to identify the pharmacokinetics of PEGasparaginase in infants with newly diagnosed ALL and gather insight into the clearance and dosing of this population.
Acute leukemia continues to be a major cause of death from disease worldwide and current chemotherapeutic agents are associated with significant morbidity in survivors. While better and safer treatments for acute leukemia are urgently needed, standard drug development pipelines are lengthy and drug repurposing therefore provides a promising approach.
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.
Copy 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.
Rishi S. Laurence Sébastien Kotecha Cheung Malinge MB ChB (Hons) MRCPCH FRACP PhD BPharm (Hons) MBA PhD PhD Co-Head, Leukaemia Translational Research
Sébastien Malinge PhD Laboratory Head, Translational Genomics in Leukaemia, Senior Research Fellow (University of Western Australia), Adjunct Senior
Laurence Rishi S. Sébastien Cheung Kotecha Malinge BPharm (Hons) MBA PhD MB ChB (Hons) MRCPCH FRACP PhD PhD Co-Head, Leukaemia Translational Research
Dr Laurence Cheung is doing everything he can to end the threat of childhood leukemia. His research has the potential to change countless lives, but he also has another important job – being a dad to three beautiful children.
B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric cancer. Current therapeutic regimens have improved 5-year event-free survival rates to 90%, however clinical outcomes for high-risk subgroups, such as BCR-ABL1+ B-ALL and relapsed ALL, remain poor. In addition, 16% of newly diagnosed children with ALL present with vertebral compression fractures. Moreover, 16% of children with ALL undergoing glucocorticoid therapy also experience a high incidence of vertebral fractures, indicating that bone health may be compromised by both leukemia progression and osteotoxicity of chemotherapy.
Mesothelioma is a cancer derived from mesothelial cells, most commonly arising from the pleura or the peritoneum. Immune checkpoint therapy (ICT) has shown survival benefit for pleural mesothelioma, but little is known about the response in peritoneal mesothelioma. Most preclinical mesothelioma models involve subcutaneous cancer cell implantation, which lacks the relevant tumour microenvironment of peritoneal mesothelioma and does not resemble the clinical presentation.