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.
Characterisation Of CBF Acute Myeloid Leukaemia By MicroRNA Profiling
Funder
National Health and Medical Research Council
Funding Amount
$118,956.00
Summary
Recent studies have demonstrated the existence of small pieces of previously undescribed genetic material, known as microRNAs (miRNAs), which are thought to have critical functions across various biological processes and regulatory pathways in cells. This project aims to examine the role of these miRNAs in the development of abnormal cellular proliferation that leads to leukaemia, by examining the expression of all known miRNAs in the abnormal cells of our patients with leukaemia.
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.
Eradicating Leukaemic Stem Cells By Targeting The Arginine Methyltransferase PRMT5
Funder
National Health and Medical Research Council
Funding Amount
$770,950.00
Summary
Acute leukemia is a devastating cancer arising from primitive cells in the bone marrow called stem cells. We have identified a protein (PRMT5) that is highly expressed in leukemia stem cells. Our preliminary experiments suggest that blocking the function of this protein with a novel drug can stop the growth of these cells. This project will use a variety of mouse models of acute leukemia to determine how PRMT5 keeps stem cells alive and whether this drug will be a valuable new treatment.
The Evolution Of Acute Myeloid Leukaemia By In Situ Transformation Of Haematopoietic Stem Cells
Funder
National Health and Medical Research Council
Funding Amount
$646,966.00
Summary
Acute myeloid leukaemia (AML) is a devastating form of blood cancer that can affect people of any age. The survival of patients with AML is poor and this is because the disease usually comes back after chemotherapy (this is called relapse). Fewer than half of all patients with AML can be cured. We have recently developed a new, and improved, model of AML in the lab, which we will use to test an exciting new treatment for patients with AML.
Klf5 Function In Normal And Leukaemic Haemopoiesis
Funder
National Health and Medical Research Council
Funding Amount
$609,924.00
Summary
Acute Myeloid Leukaemia (AML) is a devastating disease that affects both children and adults. New treatments that target particular genetic abnormalities are urgently needed. We have identified KLF5 as a gene that may control blood cell maturation. In AML patient samples we have found alterations of the KLF5 gene that may suppress its activity and contribute to the formation of leukaemia. These leukaemias may be good candidates for treatment with new drugs called methyltransferase inhibitors.