A5021573658- Acute Lymphoblastic Leukemia research
- Acute Myeloid Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Epigenetics and DNA Methylation
- Peptidase Inhibition and Analysis
- Pancreatic and Hepatic Oncology Research
- DNA Repair Mechanisms
- Aldose Reductase and Taurine
- Immune Cell Function and Interaction
- RNA modifications and cancer
- Cell Adhesion Molecules Research
- Hematopoietic Stem Cell Transplantation
- NF-κB Signaling Pathways
- Cannabis and Cannabinoid Research
- Immune cells in cancer
- Blood disorders and treatments
- Down syndrome and intellectual disability research
- Viral-associated cancers and disorders
- Lymphoma Diagnosis and Treatment
- Protease and Inhibitor Mechanisms
- Adenosine and Purinergic Signaling
- Cardiac Fibrosis and Remodeling
- Ubiquitin and proteasome pathways
- CAR-T cell therapy research
- Polyomavirus and related diseases
Murdoch Children's Research Institute
2015-2024
UNSW Sydney
2023-2024
Cancer Institute of New South Wales
2023-2024
Children's Cancer Institute Australia
2023
Royal Children's Hospital
2015-2019
The University of Melbourne
2015
orn et al 6 (Lund, accession no.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological malignancy with median survival of 14 months (with window 6–28 months) from diagnosis.1 BPDCN derived the precursors cells2 recognized as an independent entity myeloid neoplasms in 2016 updated World Health Organization classification.3 Although predominantly affects adults age 70s, cases involving younger children have been reported. Unique clinical presentations include skin infiltration, at...
The metalloproteinase ADAMTS-5 (A disintegrin and with thrombospondin motifs) degrades aggrecan, a proteoglycan essential for cartilage structure function. is the major aggrecanase in mouse cartilage, also likely to be humans. multidomain enzyme, but function of C-terminal ancillary domains poorly understood. We show that mutant lacking catalytic domain, full suite inhibits wild type ADAMTS activity, vitro vivo, dominant-negative manner. data suggest binds ADAMTS-5; thus we tested hypothesis...
Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) is a high-risk subtype of B-cell ALL characterized by gene expression profile resembling Philadelphia chromosome-positive (Ph+ ALL) in the absence BCR-ABL1. Tyrosine kinase-activating fusions, some involving ABL1, are recurrent drivers Ph-like and targetable with tyrosine kinase inhibitors (TKIs). We identified rare instance SFPQ-ABL1 child ALL. expressed cytokine-dependent cell lines was sufficient to transform cells these were...
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy that expresses high levels of the enzyme aldo-keto reductase family 1 member C3 (AKR1C3). To exploit this finding, we developed a novel prodrug, ACHM-025, which selectively activated by AKR1C3 to nitrogen mustard DNA alkylating agent. We show ACHM-025 has potent in vivo efficacy against T-ALL patient-derived xenografts (PDXs) and eradicated disease 7 PDXs. was significantly more effective than...
Cancer is driven by mutations of the genome that can result in activation oncogenes or repression tumour suppressor genes. In acute lymphoblastic leukemia (ALL) focal deletions IKAROS family zinc finger 1 (IKZF1) loss zinc-finger DNA-binding domains and a dominant negative isoform associated with higher rates relapse poorer patient outcomes. Clinically, presence IKZF1 informs prognosis treatment options. this work we developed method for detecting exon genes using RNA-seq application to...
T cell acute lymphoblastic leukemia (T-ALL) and lymphoma (T-LBL) are rare aggressive hematological malignancies. Current treatment consists of intensive chemotherapy, leading to 80% overall survival but associated with severe toxic side effects. Furthermore, 10-20% patients still die from relapsed or refractory disease providing a strong rationale for more specific, targeted therapeutic strategies less toxicities. Here, we report novel MYH9::PDGFRB fusion in T-LBL patient demonstrate that...
Key Points A novel KMT2A-rearrangement, MLL-TFE3, was identified in an infant leukemia patient. MLL-TFE3 expression produces aggressive a mouse model.
The quest to unlock the secrets of eternal youth or extending life span have been described throughout history. This includes ancient texts describing "fountain youth" and more recently within popular fiction series "Harry Potter" where philosopher's stone provides an "elixir life." In reality, our longevity is in part due presence effective immune system coupled with ability pre-emptively manipulate this using vaccinations. Indeed, it could be argued that vaccinations remain one most...
<title>Abstract</title> The epigenetic landscape plays a critical role in the onset and evolution of various malignancies, but its therapeutic utility remains underutilized. Glucocorticoids are an essential part many multi-agent treatment regimens for lymphoid malignancies. However, emergence glucocorticoid resistance is significant barrier to cure, which due alterations, including aberrant chromatin accessibility hypermethylation at lymphocyte-specific glucocorticoid-response elements...
The epigenetic landscape plays a critical role in cancer progression, yet its therapeutic potential remains underexplored. Glucocorticoids are essential components of treatments for lymphoid cancers, but resistance, driven part by changes at glucocorticoid-response elements, poses major challenge to effective therapies. Here we show that glucocorticoid treatment induces distinct patterns chromosomal organization glucocorticoid-sensitive and resistant acute lymphoblastic leukemia xenograft...
T-cell acute lymphoblastic leukemia (T-ALL) is a rare and aggressive hematologic malignancy affecting both children adults. 1,2 T-ALL subtype identification an emerging area of active research; as recently 2016, the World Health Organization suggested only 1 provisional distinct classification: early precursor (ETP). 3wever, recent revisions by International Consensus Classification in 2022 further subclassified ETP based on BCL11B deregulation while introducing 8 classifications for non-ETP...
Abstract B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer. Subtypes within B-ALL are distinguished by characteristic structural variants and mutations, which in some instances strongly correlate with responses to treatment. The World Health Organisation (WHO) recognises seven distinct classifications, or subtypes , as of 2016. However, recent studies have demonstrated that can be segmented into 23 based on a combination genomic features gene expression...
Mutations within the IL7-R-JAK-STAT signaling pathway are important drivers of T-cell acute lymphoblastic leukemia (T-ALL). Here we describe steps required to generate retroviral particles for stable expression mutant JAK3 constructs that induce constitutive JAK/STAT signaling. These subsequently used viral transduction IL-3 cytokine-dependent Ba/F3 cell line or murine hematopoietic stem and progenitor cells (HSPCs) in vitro vivo modelling cytokine-independent growth initiation respectively.
Abstract Cancer is driven by mutations of the genome that can result in activation oncogenes or repression tumour suppressor genes. In acute lymphoblastic leukemia (ALL) focal deletions IKAROS family zinc finger 1 (IKZF1) loss zinc-finger DNA-binding domains and a dominant negative isoform associated with higher rates relapse poorer patient outcomes. Clinically, presence IKZF1 informs prognosis treatment options. this work we developed method for detecting exon genes using RNA-seq...