Role Of ZEB/NuRD Interactions In Haematopoiesis And Lymphoid Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$810,497.00
Summary
Cancers of the blood arise from (epi)genetic changes that enable blood cells to bypass normal survival and growth checkpoints, leading to accumulation of additional mutations that drive full-scale transformation. This grant aims to understand the role of specific transcription factors (that control disease causing genes to be expressed) and how we can use a novel class of epigenetic drugs together with inhibition of these factors to selectively get rid of cancer causing blood cells in the body.
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.
Roles Of The EMT Transcription Factors In Epigenetic Remodelling And Myeloid Cell Transformation.
Funder
National Health and Medical Research Council
Funding Amount
$809,520.00
Summary
This project is based upon our novel discoveries that identified ZEB2 and SNAI1 as novel genes involved in the development of aggressive forms of blood cancer. During the course of this proposal we will find new drug targets and new drug treatment options using existing drugs that will specifically target cancer initiating cells in order to kill aggressive forms of blood cancers that are currently refractory to treatment.
‘Transcriptional Tumour Suppression’ By Pax5 And Ikaros In B Progenitor Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$558,927.00
Summary
B-progenitor acute lymphoblastic leukaemia (B-ALL) is the most common cancer in children. The genes Pax5 and Ikaros are frequently mutated in B-ALL, but how this contributes to leukaemia development and treatment resistance remains unclear. We have recently produced new B-ALL models driven by reversible suppression of Pax5 or Ikaros activity, and propose to use these models to uncover how these genes control leukaemia differentiation and regression.
Role Of Erg In B-cell Acute Lymphoblastic Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$749,034.00
Summary
Acute lymphoblastic leukaemia (ALL) is a lethal blood cancer for which current treatments are suboptimal. Over-expression of the ERG gene has been associated with the poor prognosis B cell ALL called Ph+ B-ALL. We have recently shown that loss of Erg prevents disease development in disease models. We hypothesise that expression of ERG is a key driver of Ph+ B-ALL and propose to define this role and identify new opportunities for development of specific novel therapeutics.
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.
Tumour Suppressive Mechanisms Of CEBP? And PU.1 In Acute Myeloid Leukemia
Funder
National Health and Medical Research Council
Funding Amount
$497,827.00
Summary
Acute myeloid leukaemia (AML) is an aggressive leukaemia with poor overall responses to therapy. The transcription factors CEBPA and PU.1 are often lost during AML development, and therapies that can restore their normal functions hold great promise. By identifying the genes that these transcription factors regulate in normal and leukaemic white blood cells, this project aims to understand how AML develops and which genes represent rational drug targets for this disease.
Defining The Leukaemogenic Mechanism For GATA2 T354M, A New Predisposing Mutation In Familial MDS/AML
Funder
National Health and Medical Research Council
Funding Amount
$631,883.00
Summary
A successful approach for identification of cancer genes has been to study the 5-10% of cases occurring in families with inherited predisposition to develop cancer. Unlike solid tumours, few cancer-causing mutations are known for haematological cancers. We have found a new mutation in 3 families in a gene (GATA2) not previously associated with familial acute myeloid leukaemia. We will explore how this mutation causes leukaemia to help better understand the more common non-inherited leukaemias.
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.
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.