A Transcription Factor Network Constraining The Development Of B Cell Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$617,531.00
Summary
B cell leukemias are relatively common, often aggressive hematopoietic malignancies and their cause is unknown in many cases. We have found that deficiencies in several transcription factors that normally control B cell differentiation cause B cell leukemias at a high frequency. We wish to identify the key pathways that are regulated by these factors and, in normal cells, prevent leukemic transformation. This will help to identify potential targets for therapeutic intervention.
Identification And Erradication Of Pre-malignant B Cells In The Prevention Of Lymphoma
Funder
National Health and Medical Research Council
Funding Amount
$607,771.00
Summary
B Cell Lymphoma is the most frequent type of non-Hodgkin lymphoma in adults and despite improved treatment, 40-50% of patients succumb to their disease. T cells are critical in the in the prevention B cell lymphoma development. In this project we aim to identify the earliest stages of B cell lymphoma and mechanisms of escape from T cell control with the ultimate aim to translate these findings to human studies to improve disease diagnosis, treatment and prognosis.
Use Of Circulating Tumour DNA To Characterise The Mutational Landscape Of Marginal Zone Lymphoma, Monitor Treatment Response And Detect Emergence Of Resistance
Funder
National Health and Medical Research Council
Funding Amount
$128,224.00
Summary
Marginal zone lymphoma (MZL) is a subtype of B-cell non-Hodgkin lymphoma for which the molecular drivers of disease are poorly understood. We hypothesise that circulating tumour DNA may be ideal for characterising the genetic mutations that underpin MZL, monitoring treatment response and detecting emergence of resistance. This non-invasive method of disease monitoring has the potential to transform management of cancers such as MZL, identify new treatment options and improve survival outcomes.
Understanding the mechanisms in the development of mutations in cancers will assist in development of targeted therapies to overcome chemotherapy resistance. The recently discovered TMPRSS2:ERG fusion in prostate cancer is unique as dominant fusion translocations are uncommon in solid organ malignancy. Activation induced cytidine deaminase (AID) is thought to play a role. Understanding the role of AID and downstream DNA repair pathways may be a target for future therapies in cancer.
RNA Polymerase I: A Novel Target In The Treatment Of MYC Driven Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$605,963.00
Summary
Synthesis of ribosomes, the cellular protein synthetic machinery, is dysregulated during cancer leading to the hypothesis that it may be causative in the malignant process. This application will test this hypothesis using novel inhibitors or ribosome biogenesis in a mouse genetic model termed E�-MYC that faithfully that replicates human B-cell lymphoma. These studies will uncover novel mechanisms in malignant transformation and identify new therapeutics in the treatment of human cancer.