Cancer is the result of multiple genetic errors, involving both the overactivity of growth-stimulating oncogenes and the loss of tumour suppressor genes. The identification of the genes in both of these categories is important if we are to understand and intervene in the disease. Tumour suppressors are the more difficult to identify, precisely because they are lost in cancer cells. Normally the task is extremely time consuming, tedious and expensive. We have developed a system which will provide ....Cancer is the result of multiple genetic errors, involving both the overactivity of growth-stimulating oncogenes and the loss of tumour suppressor genes. The identification of the genes in both of these categories is important if we are to understand and intervene in the disease. Tumour suppressors are the more difficult to identify, precisely because they are lost in cancer cells. Normally the task is extremely time consuming, tedious and expensive. We have developed a system which will provide a short-cut to the cloning of one such gene. We have started with the mouse version, which is lost in leukemic cells. We have mapped the gene to within a very small chromosomal region, and we have identified a biological effect which correlates with loss of the gene. Our next step is to combine these two approaches to clone the gene. Because these genes are always highly conserved between species, we will be able to quickly clone the corresponding human gene, the loss of which is very likely to be important in cancer of various types.Read moreRead less
Molecular Analysis Of Myelodysplasia In The Nup98HoxD13 Mouse Model
Funder
National Health and Medical Research Council
Funding Amount
$351,502.00
Summary
Myelodysplastic syndrome is a preleukemic condition which is poorly understood and occuring at an increasing frequency. Unfortunately no targeted therapy exists. Two features of the disease are abnormal gene expression and abnormal cell death. We have a uniquely accurate model of this disease, and we plan to use it to investigate these two phenomena which will lead to greater understanding of the disease and new molecular targets for therapeutic agents to be developed and tested in our model.
Acute Lymphoblastic Leukemia And The Bone Marrow Microenvironment
Funder
National Health and Medical Research Council
Funding Amount
$420,872.00
Summary
This research aims to identify new drugs for the treatment of childhood and adult acute lymphoblastic leukemia (ALL). We have identified drugs that interfere with interactions between the bone marrow and leukemic cells and hypothesise that these will increase the potency of currently used chemotherapy. We will test these agents in animal models of human leukemia. By analysing the effects of these new drugs we will also understand how we can further improve treatments.
Transcriptional Complexes In Haematopoiesis And T-cell Leukemia
Funder
National Health and Medical Research Council
Funding Amount
$557,939.00
Summary
Childhood T-cell leukemias have a poor prognosis for recovery. We are determining, with atomic level precision, how the proteins LMO2 (also linked to prostate and other cancers) and Tal1, and their binding partners contribute to both normal blood cell development and T-cell leukemia. With this information we are developing reagents that can be used to disrupt disease-causing complexes, and which will lead towards the development of new, specific, therapeutics for leukemias and other cancers.
The Role Of A Phosphorylated Ser/Tyr Bidentate Motif In Leukemia And Myeloproliferative Disorders
Funder
National Health and Medical Research Council
Funding Amount
$279,254.00
Summary
The ability of a normal cell to survive and grow is subject to tight control. Cancer cells escape both these controls and survive and grow in an deregulated manner. Many therapies that are in clinical use or in pre-clinical development target the growth of cancer cells. While such an approach has the advantage of being highly effective in stopping the advance of cancer cell growth, it may allow the long-term survival of some cancer cells and increase the possibility that these cells will become ....The ability of a normal cell to survive and grow is subject to tight control. Cancer cells escape both these controls and survive and grow in an deregulated manner. Many therapies that are in clinical use or in pre-clinical development target the growth of cancer cells. While such an approach has the advantage of being highly effective in stopping the advance of cancer cell growth, it may allow the long-term survival of some cancer cells and increase the possibility that these cells will become resistant to drug treatment leading to disease relapse. On the other hand, therapies that target the survival of malignant cells would be expected to pull the rug from underneath cancer by killing the malignant cells regardless of whether they are growing or not. We have identified a signalling device in normal blood cells that controls both the growth and survival of cells. This device is in effect a switch with 2 components both of which are normally turned on and off. These 2 components are differentially wired to to the cell transmitting unique signals. Importantly, we have found that this switch is faulty in blood cancers and is permanently on in some leukemias promoting their prolonged life-span. Targetting specific components of this unregulated switch may provide new and improved approaches for the development of therapeutics in the treatment of leukemia.Read moreRead less
Regulatory Dendritic Cells For The Prevention And Treatment Of Graft-versus-Host Disease.
Funder
National Health and Medical Research Council
Funding Amount
$165,250.00
Summary
Allogeneic bone marrow transplantation (BMT) remains the most effect curative treatment for patients with a number of malignant conditions, especially leukemia. Graft-versus-Host Disease (GVHD) ocurrs when the newly transplanted bone marrow (which includes the immune system) recognises the transplant recipient as foreign and mounts an immune attack against patient tissues. GVHD is the major complication of BMT and is responsible for the death of up to half of the patients who receive this proced ....Allogeneic bone marrow transplantation (BMT) remains the most effect curative treatment for patients with a number of malignant conditions, especially leukemia. Graft-versus-Host Disease (GVHD) ocurrs when the newly transplanted bone marrow (which includes the immune system) recognises the transplant recipient as foreign and mounts an immune attack against patient tissues. GVHD is the major complication of BMT and is responsible for the death of up to half of the patients who receive this procedure. These studies will focus on the ability of a newly defined type of white blood called a regulatory dendritic cell to prevent this complication and avoid the requirement for BMT patients to take drugs that suppress their immune system.Read moreRead less
Identification Of Novel Regulators Of Flt3 Receptor-dependent Dendritic Cell Development And Differentiation
Funder
National Health and Medical Research Council
Funding Amount
$605,043.00
Summary
Dendritic cells are specialized immune cells that play a key role in regulating the immune system. In the resting animal, their differentiation is largely regulated by signalling though the Flt3 pathway - the pathway most frequently dysregulated in leukemias. This project will generate a a detailed map of the important signals that instruct dendritic cell development along the Flt3 pathway and provide improved understanding of the cellular and molecular controls of this pathway.