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Mechanisms Of Glucocorticoid Resistance In Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Glucocorticoids are extremely active drugs used in the treatment of childhood acute lymphoblastic leukaemia (ALL), yet a proportion of patients respond poorly to therapy and exhibit resistance at relapse. Clinically relevant mechanisms of glucocorticoid resistance are poorly understood, principally due to lack of appropriate experimental models. This project will reveal novel mechanisms of drug resistance in childhood leukaemia and lead to novel therapeutic strategies to improve outcome.
New Compounds For Tailored Therapy Against MLL-rearranged Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$326,401.00
Summary
Some of the worst leukaemia survival rates are found in children and adults whose leukaemias display abnormalities of the MLL gene and alternative therapies are therefore urgently required for these patients. The aim of this project is to develop new compounds that specifically inhibit this abnormal gene and in turn inhibit the growth of these cells in the patient. In this way we hope to provide new and more effective therapies for patients affected with this aggressive type of leukaemia.
Understanding The Role Of Three-dimensional Genome Organisation In B Cell Lineage Commitment And Leukaemia.
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Every one of your nuclei contain 2 metres of DNA. This DNA is 300,000 times longer than the nucleus itself. In order to fit into this space, while maintaining access to crucial genes, the DNA forms a fantastically ordered three-dimensional structure. This intricate organisation is crucial to health, with even minute changes driving diseases, such as cancer and heart disease. We propose using new technology to understand how this organisation changes during immune cell development and leukaemia.
A New Model Of T Cell Lymphoma Induced By An Ets Transcription Factor
Funder
National Health and Medical Research Council
Funding Amount
$679,091.00
Summary
The identification of leukaemia-causing genes is crucial as once these are found new specific drugs can be developed. This is best exemplified by the new drug, Gleevec, that inhibits a leukaemia-causing gene in myeloid leukaemia. This has allowed a large reduction of high chemotherapy treatment but has induced remission in around 80% of patients. This proposal has identified a novel leukaemia-causing gene for T cell leukaemia. Therefore, new specific drugs can now be made to inhibit it.
Structure And Composition Of The Pre-T Cell Receptor-CD3 Complex
Funder
National Health and Medical Research Council
Funding Amount
$307,946.00
Summary
In order to recognize a wide variety of pathogens, humans produce many different T cell receptors (TCRs) by the process of gene-rearrangement. However, gene-rearrangement may not always lead to a functioning TCR. We are studying the pre-TCR protein that is responsible for monitoring the success of gene-rearrangement and is thus essential for the formation of a robust immune system. Understanding pre-TCR function will lead to new treatments for immune related diseases.
Role Of Connective Tissue Growth Factor In The Pathobiology Of Lymphoid Tumours And Response To Therapy
Funder
National Health and Medical Research Council
Funding Amount
$603,615.00
Summary
Leukaemia is the most common cancer in children and the improved cure rates are among the major biomedical advances of the past five decades. However, we still do not fully understand why leukaemia cells have a growth advantage. We identified the growth factor CTGF as being massively activated in leukaemia cells. The project aims to study the role of CTGF in bringing about the disease. Insights gained are expected to lead towards novel treatments for patients with leukaemia.
A Study To Evaluate Safety And Feasibility Of Administrating Zoledronic Acid To Children And Adolescents With Acute Lymphoblastic Leukemia And Lymphoma To Prevent Joint Complication.
Funder
National Health and Medical Research Council
Funding Amount
$16,231.00
Summary
Osteonecrosis (bone death) is a debilitating complication seen following chemotherapy for acute lymphoblastic leukemia in older children. It potentially could lead to destruction of joint, severely limiting quality of life and ultimately requiring joint replacement surgery. Currently there is no effective medical treatment to manage this. Based on our animal experiments we want to study if Zoledronic acid could prevent severe joint destruction in these children and improve their quality of life.
Genome-wide Epigenetic Analysis Of Childhood Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$410,469.00
Summary
Of all cancers in children, Acute Lymphoblastic Leukaemia is the most common. To date, the causal mechanism(s) for leukaemia in children remain unclear. Although 5-year event-free survival rates are relatively high (up to 80%) it is still unclear why children expected to survive with a good prognosis, succumb to the disease. Therefore, there is still a need to further refine current diagnosis and prognosis parameters that will together lead to improved outcomes to children with leukaemia.