Characterisation Of Erythropoietic Mutants Identified In A Forward Genetic Screen In Mice.
Funder
National Health and Medical Research Council
Funding Amount
$501,902.00
Summary
The human bone marrow is the pivotal organ in the replacement of the vast numbers of blood cells normally consumed each day. One of the cells regenerated by this organ are the red blood cells which are critical for the transport of oxygen to the tissues. This proposal uses genetically altered mice to identify genes that are critical for the production of normal red blood cells. Mice exposed to a chemical that induces random mutations in their genome are bred and pups with abnormal red blood cell ....The human bone marrow is the pivotal organ in the replacement of the vast numbers of blood cells normally consumed each day. One of the cells regenerated by this organ are the red blood cells which are critical for the transport of oxygen to the tissues. This proposal uses genetically altered mice to identify genes that are critical for the production of normal red blood cells. Mice exposed to a chemical that induces random mutations in their genome are bred and pups with abnormal red blood cells are identified. The responsible genetic mutation is identified and the gene is then studied to determine how it influences red blood cell production. The results of these studies provide insights into a variety of human conditions including anemia, thalassemia and sickle cell disease.Read moreRead less
Identification Of The Molecular Genetic Basis Of The Hepatic Veno-occlusive Disease With Immunodeficiency Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$224,250.00
Summary
One of the most serious complications of bone marrow transplantation is veno-occlusive disease (VOD), also termed sinusoidal obstruction syndrome (SOS). This condition occurs in 10% of transplanted patients and is characterised by abnormalities of liver function, enlargement of the liver, clotting abnormalities, fluid retention and finally failure of multiple organs and death in 30-50% of cases. The cause of VOD is unknown, and its occurrence cannot be predicted in individual patients. Eight fam ....One of the most serious complications of bone marrow transplantation is veno-occlusive disease (VOD), also termed sinusoidal obstruction syndrome (SOS). This condition occurs in 10% of transplanted patients and is characterised by abnormalities of liver function, enlargement of the liver, clotting abnormalities, fluid retention and finally failure of multiple organs and death in 30-50% of cases. The cause of VOD is unknown, and its occurrence cannot be predicted in individual patients. Eight families have been described in whom a number of individuals have succumbed to a condition which is clinically and histologically indistinguishable from VOD. Affected individuals also have a form of immunodeficiency (hence termed VODI), and the abnormalities are inherited in an autosomal recessive pattern. All eight are of Lebanese origin, suggesting that a single genetic ancestral mutation was responsible for the disorder in all families, who are distantly related. We have access to genetic material from three of these families, and are on the way to identifying the causative genetic abnormality. We hypothesise that understanding this abnormality will lead to an understanding of VOD which occurs after bone marrow transplantation. We have used 800 polymorphic genetic markers scattered throughout the genome to identify the location of the genetic abnormality, and have localised the defect to a region of chromosome 2 which contains approximately 37 known and predicted genes. We now aim to determine which of the gene(s) in the candidate region is responsible for VODI, and plan to examine DNA from individuals who have had VOD after transplantation to determine if they have a related abnormality. Finding the VODI gene will benefit these families through the availability of carrier detection and may also lead to an understanding of the veno-occlusive disease that occurs after bone marrow transplantation.Read moreRead less
We want to understand more about the control of blood cell formation and the development of leukaemia. We have discovered one gene that is very important in both these processes. It is the most common genetic abnormality involved in causing human T-cell leukaemia and we have recently shown that it is absolutely required for the development of all blood cells within an animal. We wish to take these observations further so that we can ultimately understand how a gene important in blood cell format ....We want to understand more about the control of blood cell formation and the development of leukaemia. We have discovered one gene that is very important in both these processes. It is the most common genetic abnormality involved in causing human T-cell leukaemia and we have recently shown that it is absolutely required for the development of all blood cells within an animal. We wish to take these observations further so that we can ultimately understand how a gene important in blood cell formation can also be important in causing leukaemia. To address this we will generate new models of blood cell development.Read moreRead less
Investigating The Gene And Gene Expression Differences In The Cells That Drive Leukemia Development And Relapse In Children With AML
Funder
National Health and Medical Research Council
Funding Amount
$388,612.00
Summary
Current treatments for AML are initially effective at killing the majority of leukemic cells, but the disease often comes back (relapses) due to rare cells that escape treatment and can regenerate the cancer (called leukemic stem cells or LSC for short). This project aims to determine if an individual patient has one, or many kinds of LSC and which kind of LSC is most likely to cause relapse. We believe that this knowledge will lead to new treatments that can target the cells that cause relapse.
A Phase I Study Of Autologous CD19 Specific Chimeric Antigen Receptor T-cells For Therapy Of Relapsed And Refractory B-cell Leukaemia And Lymphoma (The Auto-CAR19 Trial).
Funder
National Health and Medical Research Council
Funding Amount
$584,666.00
Summary
Most people with leukaemia and lymphoma who relapse early after chemotherapy die of their disease. Inserting special genes into immune cells can enable them to kill leukaemia and lymphoma and has led to dramatic cures, but the cost of the viral vectors used to make these cells is prohibitively expensive. We will make leukaemia and lymphoma specific immune cells from patients using an inexpensive non-viral system, then administer the immune cells to patients to assess their safety and efficacy.
A Phase I Study Of PiggyBac CD19 Specific Chimeric Antigen Receptor T-cells For Therapy Of Persistent And Relapsed B-cell Leukaemia And Lymphoma Post Allogeneic Stem Cell Transplantation (The CARTELL Study).
Funder
National Health and Medical Research Council
Funding Amount
$357,590.00
Summary
Most people with relapsed leukaemia and lymphoma after bone marrow transplant die of their disease. Inserting special genes into immune cells can enable them to kill leukaemia and lymphoma and has led to dramatic cures, but there is little experience in bone marrow transplant patients. We will make leukaemia and lymphoma specific immune cells from normal bone marrow transplant donors, then administer the immune cells to transplant patients to assess their safety and effectiveness.