Molecular Pathways Mediating Quiescence And Resistance In Leukaemia Stem Cells In Acute Myeloid Leukaemia.
Funder
National Health and Medical Research Council
Funding Amount
$100,381.00
Summary
Acute myeloid leukaemia (AML) is a devastating cancer of the blood and bone marrow which is rapidly fatal unless effectively treated with chemotherapy. AML is caused by genetic events that alter normal blood stem cells to give them a growth and survival advantage and also may confer resistance to chemotherapy in some cases. We will evaluate and target the mechanism of this resistance in laboratory models. This information can then be used to design new treatments to improve outcomes in AML.
Investigating The Molecular Basis For Drug Resistance And Disease Relapse In Myelodysplastic Syndromes
Funder
National Health and Medical Research Council
Funding Amount
$722,557.00
Summary
Myelodysplastic Syndromes (MDS) are a group of blood stem cell disorders that result in low blood counts and leukemia especially in the elderly. Azacitidine (AZA) is a drug that improves blood counts and delays progression to leukemia and is the treatment of choice. However, only half the patients treated with AZA ever respond and half of the responders relapse within a year. We will describe the origins of MDS and the basis for drug response, resistance and disease relapse.
Epigenetic Regulation Of Self-renewal Signalling Pathway In Leukemic Stem Cell Formation
Funder
National Health and Medical Research Council
Funding Amount
$885,476.00
Summary
Acute myeloid leukaemia (AML) is a fatal form of blood cancer. The survival of patients with AML remains poor and this is due to the return of disease after chemotherapy (relapse). Leukemic stem cells (LSCs) are the major cause of relapse and we study how LSCs are regulated. This will provide valuable input into the development of novel therapeutic strategies to target therapy-resistant LSCs and improve AML outcome.
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.
The Role Of MOZ In The Development Of The Hematopoietic System, Spleen And Thymus
Funder
National Health and Medical Research Council
Funding Amount
$324,375.00
Summary
Current treatment of leukaemia in adults is unsatisfactory with the majority of patients dying. In the past most treatments for cancer have been empirical, that is a particular drug has been found to be effective by trial and error rather than a process of rational design. In order to improve the rate at which effective treatments for leukaemia are found it is necessary to understand how hematopoiesis is regulated and what the critical points are where things can go wrong, leading to cancer. Som ....Current treatment of leukaemia in adults is unsatisfactory with the majority of patients dying. In the past most treatments for cancer have been empirical, that is a particular drug has been found to be effective by trial and error rather than a process of rational design. In order to improve the rate at which effective treatments for leukaemia are found it is necessary to understand how hematopoiesis is regulated and what the critical points are where things can go wrong, leading to cancer. Some genes are commonly found to be mutated in leukaemia. Clearly these genes are involved in some key aspect of regulation of hematopoiesis. We are studying one of these genes, MOZ, which is mutated in acute myeloid leukaemia. The purpose of this grant is to determine what the normal function of this gene is. One of the most promising new treatments for leukaemia is directly targeting the regulation of gene expression inside the cell. MOZ is one of the proteins, which regulates gene expression in hematopoiesis and controls the differentiation of different types of blood cells. One of the possible effects of these new types of anticancer drugs is to accentuate the normal function of MOZ. However, at the moment we don't know what the normal function of MOZ is so it is impossible to test this prediction. If we know which pathways controlling blood formation MOZ is acting in it may be possible, in the future, to use this information to improve on the current anti cancer drugs in a more directed way than has been possible in the past.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.
Lymphoid Organ Development: Synthetic Organogenesis Of Artificial Spleen And Characterisation Of Tissue-specific Hematopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$350,232.00
Summary
Spleen is an organ which filters blood circulating around the body and provides immune protection against blood-borne pathogens. Research into spleen development will attempt to synthesise artificial spleen tissue, leading to possible tissue replacement therapies or enhancement of immunity towards infection or cancer. Cellular development in spleen will also be investigated with a view to identifying novel white blood cell subsets that have potential for becoming new targets for immunotherapy.
Mechanisms Of Cytokine Independence During The Development Of Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$598,163.00
Summary
Signals from growth factors such as cytokines and hormones are required for cell survival. In their absence cells activate an in-built self-destruct process. Determining how cytokines regulate cell death will provide novel targets so that unwanted cells (like cancer cells) can be triggered to die and needed cells (such as brain cells) can survive.