Chronic Lymphocytic Leukemia (CLL) is a very common blood cancer. Leukaemic tumour cells actively shut down key immune defences in patients who are very prone to severe infections. Current chemotherapies further immuno-compromise CLL patients and over a quarter will die from an infection despite having responded to cancer treatments. We propose that restoring key immune functions in CLL is key to improve resistance to infection and restore natural anti-cancer immunity.
Investigating The Transcriptional Circuitry Of Normal Human Haematopoietic And Leukaemic Cells
Funder
National Health and Medical Research Council
Funding Amount
$698,797.00
Summary
Despite improvements in supportive care, more than half the patients diagnosed with acute myeloid leukaemia (AML) succumb to complications associated with the disease or its treatment. To improve treatment outcomes, we need to understand how leukaemic cells self-renew and how this differs from normal blood stem cells. Our proposal aims to do this by using computational and experimental methods to identify and validate factors to which leukaemic cells are more dependent than normal blood cells.
Co-operation Between GATA2 Mutation Or Expression And RAS Signalling In AML
Funder
National Health and Medical Research Council
Funding Amount
$860,601.00
Summary
We have identified a gene GATA2 which, when mutated, can lead to leukaemia (blood cancer). We will collect samples worldwide from families and individuals that carry GATA2 mutations and have developed leukaemia, and will screen for other genetic changes that contribute to leukaemia. We have also identified a novel group of patients who have a low GATA2 activity and who also have mutations in the RAS gene, a known contributor to leukaemia. We will determine how these cooperate to cause leukaemia.
Prophylactic Early Parenteral Nutrition In Patients Undergoing Hematopoietic Cell Transplantation: A Multi-centre Randomised Controlled Trial.
Funder
National Health and Medical Research Council
Funding Amount
$1,131,673.00
Summary
We intend to conduct a multi-centre clinical trial in patients receiving bone marrow transplants to determine whether very early nutrition support improves overall survival.
Exploiting And Defining The Immune Regulatory Activities Of BET Bromodomain Inhibitors
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Immune-based agents such as “checkpoint inhibitors” have the ability to re-awaken our own immune systems and activate previously dormant anti-tumour responses. We have discovered that small molecule inhibitors of gene regulatory proteins called bromodomain proteins act synergistically with checkpoint inhibitors in mouse cancer models. I will define the molecular and biological events underpinning this novel combination approach and assess the effects of the combination across different tumours.
Epigenetic Regulation Of Self-renewal Signalling Pathway In Leukemic Stem Cell Formation
Funder
National Health and Medical Research Council
Funding Amount
$885,476.00
Summary
Acute myeloid leukaemia (AML) is a fatal form of blood cancer. The survival of patients with AML remains poor and this is due to the return of disease after chemotherapy (relapse). Leukemic stem cells (LSCs) are the major cause of relapse and we study how LSCs are regulated. This will provide valuable input into the development of novel therapeutic strategies to target therapy-resistant LSCs and improve AML outcome.
Inherited determinants of cancer aetiology. Family history of cancer is a strong risk factor for many cancers. This project will aim to identify inherited factors influencing risk of developing cancer and those factors influencing the course of the disease and outcomes.
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.
Characterisation Of A New Poor-Risk Sub-Category Of Chronic Phase Chronic Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$609,320.00
Summary
The introduction of targeted therapy for chronic myeloid leukaemia (CML) has resulted in excellent responses for many patients. However, some 30-40% of patients respond very poorly to this therapy and therapeutic advances are urgently needed to improve response in these patients. In order to better treat these poor risk patients we aim, in this project, to develop a greater understanding of their disease, and from this identify specific cellular targets for future drug treatment/combination ther ....The introduction of targeted therapy for chronic myeloid leukaemia (CML) has resulted in excellent responses for many patients. However, some 30-40% of patients respond very poorly to this therapy and therapeutic advances are urgently needed to improve response in these patients. In order to better treat these poor risk patients we aim, in this project, to develop a greater understanding of their disease, and from this identify specific cellular targets for future drug treatment/combination therapy.Read moreRead less
The Role Of Thymocyte Self-renewal In Causing T Cell Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$586,594.00
Summary
Recurrence of acute leukamia after therapy is due to the presence of immature cells that can self-renew, a process that is normally restricted to stem cells. Through the study of mice that develop leukaemia, we have identified these very rare self-renewing cells that are resistant to standard therapies. We can identify and measure these cells many months before leukaemia develops. As such, we will use this mouse model to understand how these cells self-renew and how they can be killed