Long-term In Vivo Imaging Of Bone Marrow Microenvironments In Multiple Myeloma.
Funder
National Health and Medical Research Council
Funding Amount
$688,371.00
Summary
White blood cells are soldiers of the immune system. When the machinery that controls growth and death of these cells is disrupted, these cells can undergo massive expansion. This leads to the development of blood cancers such as multiple myeloma (MM). In MM, malignant cells infiltrate bones preventing production of blood and damaging the bone structure leading to fractures. Using cutting edge microcopy we will watch how MM cells grow and damage bone tissue to develop new therapeutic approaches.
Microenvironmentally Induced Acute Lymphoblastic Leukemia Cell Quiescence And Chemotherapy Evasion
Funder
National Health and Medical Research Council
Funding Amount
$672,885.00
Summary
Although almost all patients with ALL achieve a remission, a proportion of children and the majority of adults relapse following treatment. Relapse occurs as a result of a small number of malignant cells that survive chemotherapy. We have identified a population of quiescent cells that could represent this population. We believe this population is defined by its location in the bone marrow. This project will characterize this population and determine whether it is protected from chemotherapy.
Bone Marrow Macrophages: “Resident Evil” In The Establishment And Progression Of Multiple Myeloma
Funder
National Health and Medical Research Council
Funding Amount
$570,585.00
Summary
Multiple myeloma (MM) is a cancer that develops within the bone marrow (BM). To date, which cells of the BM stroma are required for the support of MM growth remains unknown. Our preliminary data suggest BM resident macrophages, expressing CD169 and CX3CR1, are essential for MM growth. Using innovative and elegant animal models of MM, we will define the role of these macrophages in MM growth and determine if macrophage-targeted therapies can delay MM growth in the relapsed disease setting.
MRNA Expression Profiling Of Chronic Lymphocytic Leukaemia (CLL) Cells From In Vivo Hypoxic Microenvironmental Niches; Applications For In Vitro Research And Clinical Management.
Funder
National Health and Medical Research Council
Funding Amount
$124,676.00
Summary
Chronic lymphocytic lymphoma (CLL) is the most frequently diagnosed leukaemia in adults and is still considered incurable. CLL cells proliferate in the lymph nodes and bone marrow; these are areas of the human body that are hypoxic when compared to blood. These hypoxic areas affect CLL cell survival, proliferation and treatment resistance. Changes that occur to CLL cells in these areas can be measured by gene expression profiling and modeled in a lab setting to identify targets for treatment.
Chemotherapy causes a massive depletion of blood-producing cells in the bone marrow. This results in a condition known as myelosuppression that has many harmful side effects for cancer patients. Our aim is to develop a safe and inexpensive approach that will specifically protect the blood-producing cells from chemotherapy but leave the cancer cells sensitive. If this treatment shows significant benefits in mouse models of cancer then the establishment of clinical trials will be initiated.
Genome-wide Epigenetic Analysis Of Childhood Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$410,469.00
Summary
Of all cancers in children, Acute Lymphoblastic Leukaemia is the most common. To date, the causal mechanism(s) for leukaemia in children remain unclear. Although 5-year event-free survival rates are relatively high (up to 80%) it is still unclear why children expected to survive with a good prognosis, succumb to the disease. Therefore, there is still a need to further refine current diagnosis and prognosis parameters that will together lead to improved outcomes to children with leukaemia.
The Targeting Of Flt3, C-Kit And Src As Therapies For C-Cbl-associated Myeloid Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$535,416.00
Summary
Most leukaemias are incurable so it is important to find new treatments. For this to occur it is essential that the mutated genes causing leukaemia are identified. We have generated a mouse with a mutation in a gene, c-Cbl, that promotes the activation of a number of proteins involved in leukaemia development. By treating c-Cbl mutant mice with drugs that target these proteins we intend to identify the most effective treatments for human leukaemias associated with c-Cbl mutations.
Screening For Recently Defined Genetic Lesions In Poor Risk Adult And Childhood ALL, And Developing Treatment Approaches To Target Causative Pathways.
Funder
National Health and Medical Research Council
Funding Amount
$744,938.00
Summary
Most adults and 20% of children with ALL relapse and die of their disease. Chromosomal changes resulting in the formation of new proteins have been recently identified in a significant number of cases. Importantly, drugs targeting these proteins are in clinical practice for other diseases. We will develop new tests to rapidly identify these patients at diagnosis, and assess the efficacy of adding these drugs to first line treatment in a clinical trial. The outcome for these patients will likely ....Most adults and 20% of children with ALL relapse and die of their disease. Chromosomal changes resulting in the formation of new proteins have been recently identified in a significant number of cases. Importantly, drugs targeting these proteins are in clinical practice for other diseases. We will develop new tests to rapidly identify these patients at diagnosis, and assess the efficacy of adding these drugs to first line treatment in a clinical trial. The outcome for these patients will likely improve significantly using this approachRead moreRead less
Role Of Endogenous Bcl-2 Family Proteins In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$474,033.00
Summary
Programmed cell death (apoptosis) is crucial for health. Impaired apoptosis can lead to cancer. In blood cancers, mutations that disrupt apoptosis allow cells to survive whilst acquiring additional mutations. Moreover, the mutations prevent most drug treatments for cancer, which act by inducing apoptosis, from working effectively. Our research will investigate the role of apoptosis in tumour development and in sustaining tumour growth. The results will help to identify new cancer therapies.
Identification of novel therapeutic targets for selectively eliminating cancer stem cells in paediatric leukaemia. Leukaemia is the most common form of cancer in children, and while the majority of children can be cured, those who relapse face a dire prognosis. It is widely believed that leukemic stem cells are responsible for relapse and this project will aim to unravel their underlying biology and identify new targets for therapeutic approaches to the disease.