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.
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.
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
Targeting Of The Myb-p300 Interaction In Myeloid Leukaemogenesis
Funder
National Health and Medical Research Council
Funding Amount
$625,980.00
Summary
MYB is a “cancer gene” which turns other genes on or off. MYB is needed by leukaemia cells but also for normal blood cell formation. This project aims to show that blocking interaction between the MYB protein and another protein called p300 is a promising strategy for leukaemia treatment, as leukaemia cells are more dependent on this interaction than normal cells. New molecules to block the MYB-p300 interaction will also be designed and tested; these may form a basis for new leukaemia drugs.
Mechanism Of Leukaemia Suppression By The Transcription Factor Ikaros
Funder
National Health and Medical Research Council
Funding Amount
$655,630.00
Summary
A subset of acute lymphoblastic leukaemias are characterised by mutations in the Ikaros gene. These leukaemias respond poorly to chemotherapy and require novel therapeutic approaches. We have discovered a new function of Ikaros in regulating leukaemia cell death. This project investigates how Ikaros regulates cell death and whether this is a general mechanism. Understanding Ikaros function is a step toward improved treatments for this aggressive type of leukaemia.
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.
Investigating The Molecular Basis For Drug Resistance And Disease Relapse In Myelodysplastic Syndromes
Funder
National Health and Medical Research Council
Funding Amount
$722,557.00
Summary
Myelodysplastic Syndromes (MDS) are a group of blood stem cell disorders that result in low blood counts and leukemia especially in the elderly. Azacitidine (AZA) is a drug that improves blood counts and delays progression to leukemia and is the treatment of choice. However, only half the patients treated with AZA ever respond and half of the responders relapse within a year. We will describe the origins of MDS and the basis for drug response, resistance and disease relapse.