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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.
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.
Identification And Characterisation Of Novel Genetic Alterations In High Risk Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$315,336.00
Summary
Acute lymphoblastic leukaemia (ALL) remains the leading cause of cancer-related death in children and young adults. The goal of this research is to identify genetic abnormalities that contribute to treatment failure in high-risk ALL. In addition to providing insights into the biologic basis of ALL, this work has the potential to result in new diagnostic tests, predict response to chemotherapy, and identify new strategies to improve the treatment outcome for ALL patients.
Targeting Drug-Resistance In Paediatric Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$649,048.00
Summary
Leukaemia is the most common type of cancer in children but resistance to therapy continues to be a significant problem. This project will investigate the biology of drug-resistance and relapse using a mouse model that replicates the human disease. We hope to identify novel therapeutic targets that can be used in combination with existing therapies to improve outcomes in this disease, particularly for patients that develop drug-resistance such as those at the time of relapse.
Translational Research Program To Advance Clinical Outcomes In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$418,192.00
Summary
Five-year survival in acute myeloid leukaemia (AML) is only 27%, placing it amongst the worst-ranked cancers for clinical outcome. Improved patient outcomes will be achieved through implementation of a Translational Research Program to support novel agent drug testing, early-phase and randomised clinical trials and a national clinical registry to audit outcomes. New insights into leukaemic stem cell function and mechanisms of drug resistance will inform the design of future clinical trials.
Overcoming The Differentiation Block In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$811,669.00
Summary
Acute myeloid leukaemia (AML) is an aggressive leukaemia with poor overall survival. About 50% of AML cases have genetic mutations that disable PU.1, which in turn alters the expression of many other genes that cause leukaemia. We have developed new AML models allowing reversible inhibition of PU.1, and have shown that re-engaging PU.1 function causes AML regression. This project aims to understand PU.1 functions in AML and identify rational drug targets for treatment-resistant disease.
GADD45A Promoter Methylation And Poor Prognosis In AML:mechanism And Clinical Significance
Funder
National Health and Medical Research Council
Funding Amount
$706,280.00
Summary
DNA methylation associated with the GADD45A gene defines an AML patient group with poor overall survival and limited treatment options. We will investigate the significance of this modification for the response of AML cells to chemotherapy and dissect the mechanism associated with this event. To translate these findings into the clinic we will test whether these patients are responsive to new agents targeting DNA methylation, and investigate survival of patients in a large independent cohort
Transposon Mutagenesis For Discovery Of Disease Causing Genes And Their Cooperative Interactions In Acute Myeloid Leukemia
Funder
National Health and Medical Research Council
Funding Amount
$659,302.00
Summary
The emergence of cancer is caused by multiple mutations in normal cells. Recent progress has allowed the detection of virtually all mutations in a cancer genome. Although this has been enormous progress, it has become increasingly evident that only rare mutations are responsible for sustained tumour growth and treatment failure, while the majority of mutations are without effect. Our research will assist identification of the genetic changes essential to leukemia development, which will help dev ....The emergence of cancer is caused by multiple mutations in normal cells. Recent progress has allowed the detection of virtually all mutations in a cancer genome. Although this has been enormous progress, it has become increasingly evident that only rare mutations are responsible for sustained tumour growth and treatment failure, while the majority of mutations are without effect. Our research will assist identification of the genetic changes essential to leukemia development, which will help develop new cancer therapies.Read moreRead less
Discovery Of New Targets For Therapy That Kills Non-dividing Cancer Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$375,828.00
Summary
I am a clinical haematologist that specialises in treating patients with a terrible form of blood cancer, acute myeloid leukaemia. Survival rates for this disease have not changed for 30 years and we now realise this is because we are not targetting the queen bee of the cancer - the cancer stem cell. In this project I am looking for cell markers that are only present in rare, truly latent non-dividing cancer stem cells effectively change a remission into a cure.
Understanding The Multistep Pathogenesis Of T-cell Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$701,992.00
Summary
Lmo2 is a transcription factor whose overexpression is a common cause of T-cell leukaemia. This project seeks to identify downstream targets of Lmo2 that cause T-cell leukemia. In addition, the origins and effects of secondary mutations that collaborate with Lmo2 in causing T-cell leukaemia will be determined. This will improve our understanding of how T-cell leukaemia develops and provide new molecular targets for therapy.