Antigen Receptor As Oncogene: Understanding CARD11 Mutations In B Cell Malignancy
Funder
National Health and Medical Research Council
Funding Amount
$607,395.00
Summary
More than 5000 Australians are newly diagnosed as lymphomas. Recent technology identified many candidate genes for lymphomas, however it still remains unclear how each mutated gene distorts signalling molecules inside tumours cells. By introducing one of recurrent mutated genes, CARD11 into mouse B cells, we will examine how this mutation affects normal signalling pathways and B cell functions. We hope this project will provide a guidance to use forthcoming drugs to target specific molecules.
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 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.
The Role Of The Homeobox Transcription Factor Hhex In Haematopoiesis And Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$623,112.00
Summary
We have shown that the Haematopoietically expressed homeobox (Hhex) protein plays important roles in development of immune cells. In addition, Hhex is required for development and maintenance of Acute Myeloid Leukemia (AML). This project will further investigate the requirement of Hhex in human AML, potentially identifying a new therapeutic target in this poor-prognosis cancer subtype. In addition, we will identify critical cofactors and targets of Hhex, revealing new therapeutic strategies.
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.
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.
Role Of Connective Tissue Growth Factor In The Pathobiology Of Lymphoid Tumours And Response To Therapy
Funder
National Health and Medical Research Council
Funding Amount
$603,615.00
Summary
Leukaemia is the most common cancer in children and the improved cure rates are among the major biomedical advances of the past five decades. However, we still do not fully understand why leukaemia cells have a growth advantage. We identified the growth factor CTGF as being massively activated in leukaemia cells. The project aims to study the role of CTGF in bringing about the disease. Insights gained are expected to lead towards novel treatments for patients with leukaemia.