A5064752314- Acute Myeloid Leukemia Research
- Chronic Lymphocytic Leukemia Research
- Lymphoma Diagnosis and Treatment
- Chronic Myeloid Leukemia Treatments
- Genomic variations and chromosomal abnormalities
- PI3K/AKT/mTOR signaling in cancer
- PARP inhibition in cancer therapy
- Acute Lymphoblastic Leukemia research
- Prenatal Screening and Diagnostics
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- RNA Research and Splicing
- Cancer-related Molecular Pathways
- Ovarian cancer diagnosis and treatment
- Genomics and Chromatin Dynamics
- Genomics and Rare Diseases
- Chromosomal and Genetic Variations
- Chromatin Remodeling and Cancer
- Protein Degradation and Inhibitors
- Retinoids in leukemia and cellular processes
- DNA Repair Mechanisms
- Histone Deacetylase Inhibitors Research
- Viral-associated cancers and disorders
- Cancer Mechanisms and Therapy
Murdoch Children's Research Institute
2020-2025
Victorian Clinical Genetics Services
2020-2025
Royal Women's Hospital
2025
The University of Melbourne
2012-2024
University of Wisconsin–Madison
2024
Hanover College
2024
Monash University
2010-2024
Royal Children's Hospital
2020-2024
Neuroscience Research Australia
2024
UNSW Sydney
2024
SummaryIncreased transcription of ribosomal RNA genes (rDNA) by Polymerase I is a common feature human cancer, but whether it required for the malignant phenotype remains unclear. We show that rDNA can be therapeutically targeted with small molecule CX-5461 to selectively kill B-lymphoma cells in vivo while maintaining viable wild-type B cell population. The therapeutic effect consequence nucleolar disruption and activation p53-dependent apoptotic signaling. Human leukemia lymphoma lines...
In addition to promoting translation, AKT also stimulates protein synthesis and cell growth by enhancing ribosome biogenesis.
Amplification of cyclin E1 (CCNE1) is associated with poor outcome in breast, lung, and other solid cancers, the most prominent structural variant primary treatment failure high-grade serous ovarian cancer (HGSC). We have previously shown that CCNE1-amplified tumors show amplicon-dependent sensitivity to CCNE1 suppression. Here, we explore targeting CDK2 as a novel therapeutic strategy cancers mechanisms resistance.We examined effect suppression using RNA interference small-molecule...
PURPOSE Nucleophosmin 1 ( NPM1) mutations are associated with a favorable prognosis in acute myeloid leukemia (AML) when an internal tandem duplication (ITD) the fms-related tyrosine kinase 3 gene FLT3) is absent FLT3-ITD neg ) or present low allelic ratio ). The 2017 European LeukemiaNet guidelines assume this true regardless of accompanying cytogenetic abnormalities. We investigated validity assumption. METHODS analyzed associations between karyotype and outcome intensively treated...
BackgroundGenomic sequencing technology allows for identification of reproductive couples with an increased chance, as compared that in the general population, having a child autosomal recessive or X-linked genetic condition.MethodsWe investigated feasibility, acceptability, and outcomes nationwide, couple-based carrier screening program Australia part Mackenzie's Mission project. Health care providers offered to persons before pregnancy early pregnancy. The results obtained from testing at...
Introduction Newborn bloodspot screening (NBS) is a highly successful public health programme that uses biochemical and other assays to screen for severe but treatable childhood-onset conditions. Introducing genomic sequencing into NBS programmes increases the range of detectable conditions raises practical ethical issues. Evidence from prospectively ascertained cohorts required guide policy future implementation. This study aims develop, implement evaluate (gNBS) pilot programme. Methods...
Loss of c-MYC is required for downregulation ribosomal RNA (rRNA) gene (rDNA) transcription by Polymerase I (Pol I) during granulocyte differentiation. Here, we demonstrate a robust reduction Pol loading onto rDNA that along with depletion the MYC target upstream binding factor (UBF) and switch from epigenetically active to silent accompanies this reduction. We hypothesized may coordinate these mechanisms via direct regulation multiple components apparatus. Using expression arrays identified...
Several novel therapeutics are poised to change the natural history of chronic lymphocytic leukaemia (CLL) and increasing use these therapies has highlighted limitations traditional disease monitoring methods. Here we demonstrate that circulating tumour DNA (ctDNA) is readily detectable in patients with CLL. Importantly, ctDNA does not simply mirror genomic information contained within malignant lymphocytes but instead parallels changes across different compartments following treatment...
Complex karyotype (CK) identified by chromosome-banding analysis (CBA) has shown prognostic value in chronic lymphocytic leukemia (CLL). Genomic arrays offer high-resolution genome-wide detection of copy-number alterations (CNAs) and could therefore be well equipped to detect the presence a CK. Current knowledge on genomic CLL is based outcomes single center studies, which different cutoffs for CNA calling were used. To further determine clinical utility assessment diagnostics, we...
MYC deregulation is common in human cancer. IG-MYC translocations that are modeled Eμ-Myc mice occur almost all cases of Burkitt lymphoma as well other B-cell lymphoproliferative disorders. Deregulated expression results increased mTOR complex 1 (mTORC1) signaling. As tumors with mTORC1 activation sensitive to inhibition, we used everolimus, a potent and specific inhibitor, test the requirement for initiation maintenance lymphoma. Everolimus selectively cleared premalignant B cells from bone...
Abstract Sorafenib maintenance improves outcomes after hematopoietic cell transplant (HCT) for patients with FMS-like tyrosine kinase 3–internal tandem duplication (FLT3-ITD) acute myeloid leukemia (AML). Although promising have been reported sorafenib plus intensive chemotherapy, randomized data are limited. This placebo-controlled, phase 2 study (ACTRN12611001112954) 102 (aged 18-65 years) 2:1 to vs placebo (days 4-10) combined induction: idarubicin 12 mg/m2 on days 1 3 either cytarabine...
BACKGROUND Myelodysplastic syndromes (MDS) appear to be underreported cancer registries, with important implications for and transfusion support service planning delivery. Two population‐based databases were linked estimate MDS incidence more accurately. METHODS Data from the statewide Victorian Cancer Registry (VCR) Admitted Episode Dataset (VAED, capturing all inpatient admissions), in Australia, linked. Incidence rates calculated based on VCR reported cases using additional identified...