Tumour B-cells From Lymphomas Are Resistant To ATP-mediated Apoptosis Due To Non-functional P2X7 Receptors
Funder
National Health and Medical Research Council
Funding Amount
$226,320.00
Summary
Adenosine triphosphate (ATP) is an important constituent normally present inside cells. When added to normal lymphocytes (or released by cells lining the vessel wall or in lymph nodes), ATP acts from outside these cells to open a pore as well as activate an enzyme which digests the lipid envelope of the cell. This loss of lipid covering of the cell produces a leakiness to various constituents of the cell which gradually leads to death of normal lymphocytes. However in the malignant lymphocytes o ....Adenosine triphosphate (ATP) is an important constituent normally present inside cells. When added to normal lymphocytes (or released by cells lining the vessel wall or in lymph nodes), ATP acts from outside these cells to open a pore as well as activate an enzyme which digests the lipid envelope of the cell. This loss of lipid covering of the cell produces a leakiness to various constituents of the cell which gradually leads to death of normal lymphocytes. However in the malignant lymphocytes of human lymphomas this mechanism of cell death does not operate. The loss of function of this 'death receptor' explains why in the lymphomas there is a progressive accumulation of malignant lymphocytes which give enlargement of lymph nodes and spleen and leads to death of the patient. Knowledge of the defect in this pathway of cell death will enable new strategies to be introduced to control this malignant disease.Read moreRead less
In Australia seventeen persons are diagnosed with leukemia or a related blood disorder each day. An understanding of the way the body controls blood cell production has widespread relevance to diseases like leukemia and the way that they are treated. The burden of this disease on the Australian health budget will continue to increase dramatically as our population ages in coming years. Moreover, an understanding of blood cell production has wider relevance to similar control mechanisms in other ....In Australia seventeen persons are diagnosed with leukemia or a related blood disorder each day. An understanding of the way the body controls blood cell production has widespread relevance to diseases like leukemia and the way that they are treated. The burden of this disease on the Australian health budget will continue to increase dramatically as our population ages in coming years. Moreover, an understanding of blood cell production has wider relevance to similar control mechanisms in other organs, as nature reuses its best inventions. Australia has had an enviable international record in discoveries related to factors controlling blood cells and we wish to continue that tradition by examining an exciting new development involving microRNAs. These molecules are found in all normal cells but they have been ignored until recently. Although the field is in its infancy, we now know that these microRNAs are likely to be involved in many cellular processes. In this project we will study the importance of this new class of regulatory molecule in order to discover previously-hidden functions in normal blood cells and their malignant counterparts (leukemias) in humans. The team comprises two laboratories which have collaborated for many years and already a number of exciting molecular methods have been developed. Ultimately this project may lead to novel treatments involving gene therapy, bone marrow transplantation and blood hormones.Read moreRead less
Dissecting FLT3 Signalling In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$498,328.00
Summary
Each year approximately 6000 Australian adults and children are diagnosed with leukaemia, lymphoma or a related blood disorder, accounting for about 15% of all cancers. Acute Myeloid Leukaemia (AML) is the most common form of leukaemia in adults resulting from an accumulation of immature myeloid cells in the bone marrow and peripheral blood as a result of sustained, abnormal cell growth and survival together with a block in normal blood cell formation. There is still a major research effort aime ....Each year approximately 6000 Australian adults and children are diagnosed with leukaemia, lymphoma or a related blood disorder, accounting for about 15% of all cancers. Acute Myeloid Leukaemia (AML) is the most common form of leukaemia in adults resulting from an accumulation of immature myeloid cells in the bone marrow and peripheral blood as a result of sustained, abnormal cell growth and survival together with a block in normal blood cell formation. There is still a major research effort aimed at understanding the mechanisms that lead to AML formation and it is clear that multiple AML oncogenes and tumour suppressors remain to be identified. Identification of further events involved in AML is important as it will provide avenues for more specific and less toxic treatments. These are needed because current success rates for AML remain relatively poor. It is critical that research into the understanding of the pathways and events involved in AML keeps pace with the rapid development of new approaches for therapeutic agents. Together this will greatly increase the scope for therapeutic intervention over the next decade. In this application we investigate the role of a new molecular pathway in AML. Our studies have identified a gene of particular interest that we propose normally prevents AML formation and therefore is frequently turned off by the cellular changes that lead to AML. We propose that silencing of this gene is particularly important in those AML cases which have mutations in the cell surface receptor FLT3 (about 30% of AML cases). We will use a number of molecular and cell biology approaches to manipulate this gene in mouse cell lines, normal mouse cells and human AML cells. A better understanding of the role of this gene and the associated pathway involving FLT3 may generate new leads for therapeutic approaches.Read moreRead less