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.
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.
Molecular Understanding Of Combination Epigenetic Therapy In MLL-fusion Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$624,660.00
Summary
The poor prognosis conferred by chromosome breaks involving the MLL gene in acute leukaemia has not significantly changed in over twenty years. This fact highlights the urgent need to identify and develop novel therapeutic agents for this disease. This project will aim to understand the mechanisms leading to the initiation and maintenance of this aggressive disease. We will then use these insights to develop a rational combination of therapeutic agents.
Reconstructing Transcriptional Networks In Leukaemic Cells
Funder
National Health and Medical Research Council
Funding Amount
$760,060.00
Summary
Cancer stem cells adopt properties of normal stem cells to survive and proliferate in the body. If we are to eradicate cancer stem cells without eradicating normal stem cells, it is of fundamental importance to recognize and target biological differences that exist between these cells. Our aim is to first understand how ‘stemness’ is maintained in normal and leukaemic cells with the ultimate objective of dismantling ‘stemness’ in the latter whilst preserving it in the former.
Investigating The Transcriptional Circuitry Of Normal Human Haematopoietic And Leukaemic Cells
Funder
National Health and Medical Research Council
Funding Amount
$698,797.00
Summary
Despite improvements in supportive care, more than half the patients diagnosed with acute myeloid leukaemia (AML) succumb to complications associated with the disease or its treatment. To improve treatment outcomes, we need to understand how leukaemic cells self-renew and how this differs from normal blood stem cells. Our proposal aims to do this by using computational and experimental methods to identify and validate factors to which leukaemic cells are more dependent than normal blood cells.
Defining The Myb-p300 Dependent Transcriptional Program In Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$603,632.00
Summary
MYB is a “cancer gene” which turns other genes on or off. MYB is needed by leukaemia cells but also for normal blood cell formation. We have found that interaction between the MYB protein and a protein called p300 is more critical for growth of leukaemia cells than for normal cells. Here we aim to identify a set of MYB/p300 co-regulated genes that are needed by leukaemia cells for the continued growth or survival. Some of these genes may be targets for developing new leukaemia drugs.
Intron Retention Regulation In Granulopoiesis And Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$574,419.00
Summary
Our project will shed light on the development of white blood cells, and what goes wrong when they become cancerous. In particular we have uncovered an unexpected control mechanism of gene expression in these cells. This mechanism governs the specific removal of molecules involved in transmitting information in cells (mRNAs). By extending our research to a cancer of white blood cells called chronic myeloid leukaemia, we hope to provide new insights into its causes and discover targets for innova ....Our project will shed light on the development of white blood cells, and what goes wrong when they become cancerous. In particular we have uncovered an unexpected control mechanism of gene expression in these cells. This mechanism governs the specific removal of molecules involved in transmitting information in cells (mRNAs). By extending our research to a cancer of white blood cells called chronic myeloid leukaemia, we hope to provide new insights into its causes and discover targets for innovative drugs.Read moreRead less