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Hypoxia impairs decitabine-induced expression of HLA-DR in acute myeloid leukaemia cell lines.
Clin Epigenetics
January 2025
School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, 2308, Australia.
Background: Hypomethylating agents (HMA), such as azacytidine (AZA) and decitabine (DAC), are epigenetic therapies used to treat some patients with acute myeloid leukaemia (AML) and myelodysplastic syndrome. HMAs act in a replication-dependent manner to remove DNA methylation from the genome. However, AML cells targeted by HMA therapy are often quiescent within the bone marrow, where oxygen levels are low.
View Article and Find Full Text PDFPersonalized Dynamic Prediction Model for Biopsy Timing in Patients With Prostate Cancer During Active Surveillance.
JAMA Netw Open
January 2025
Erasmus MC Cancer Institute, University Medical Center Rotterdam, Rotterdam, the Netherlands.
Importance: Active surveillance (AS) for patients with prostate cancer (PC) often includes fixed repeat prostate biopsies that do not account for the varying risk of reclassification to significant disease. Given the invasive nature and potential complications of biopsies, a personalized approach is needed to balance the burden of biopsies with the risk of missing disease progression.
Objective: To develop and externally validate a dynamic model that predicts an individual's risk of PC reclassification during AS.
CD19-directed chimeric antigen receptor-engineered (CD19 CAR) T-cell therapy elicits high response rates but fails to induce durable responses in most adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). In a previous clinical trial (NCT01865617), we observed anti-CAR immune responses associated with impaired in vivo CAR T-cell expansion after second infusions. Because these CD8+ T-cell responses were predominantly directed at peptides derived from the murine single chain variable fragment (scFv) in the CAR, we conducted a clinical trial investigating the safety and efficacy of CD19 CAR T-cells engineered with a CAR incorporating a fully human scFv (JCAR021) in adults with R/R B-ALL (NCT03103971).
View Article and Find Full Text PDFIntegrating post-validation surveillance of lymphatic filariasis with the WHO STEPwise approach to non-communicable disease risk factor surveillance in Niue, a study protocol.
PLoS One
January 2025
Centre for Clinical Research, The University of Queensland, Brisbane, QLD, Australia.
Background: Lymphatic filariasis (LF), a mosquito-borne parasitic disease caused by three species of filarial worms, was first detected in Niue, a small Pacific Island nation of approximately 1,600 people, in 1954. After extensive efforts involving multiple rounds of Mass Drug Administration, Niue was validated by the World Health Organization (WHO) as having e4liminated LF as a public health problem in 2016. However, no surveillance has been conducted since validation to confirm infection rates have remained below WHO's elimination threshold.
View Article and Find Full Text PDFA triad of somatic mutagenesis converges in self-reactive B cells to cause a virus-induced autoimmune disease.
Immunity
January 2025
Garvan Institute of Medical Research, Darlinghurst, NSW, Australia; St Vincent's Clinical School, UNSW Sydney, Sydney, NSW, Australia. Electronic address:
The unexplained association between infection and autoimmune disease is strongest for hepatitis C virus-induced cryoglobulinemic vasculitis (HCV-cryovas). To analyze its origins, we traced the evolution of pathogenic rheumatoid factor (RF) autoantibodies in four HCV-cryovas patients by deep single-cell multi-omic analysis, revealing three sources of B cell somatic mutation converged to drive the accumulation of a large disease-causing clone. A method for quantifying low-affinity binding revealed recurring antibody variable domain combinations created by V(D)J recombination that bound self-immunoglobulin G (IgG) but not viral E2 antigen.
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