A New Therapeutic Monoclonal Antibody Targeting CD302 In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$124,676.00
Summary
This project will develop a new antibody treatment for Acute Myeloid Leukaemia. Antibody treatments help the body to attack the leukaemia using its immune system. The prognosis of this leukaemia is poor. Our current treatments use high dose chemotherapy and sometimes a stem cell transplant. Many patients cannot have the current therapy due to their age or other medical problems. A new antibody therapy may be used on its own or with other therapies to help more patients achieve remission.
Overcoming The Differentiation Block In Acute Myeloid Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$811,669.00
Summary
Acute myeloid leukaemia (AML) is an aggressive leukaemia with poor overall survival. About 50% of AML cases have genetic mutations that disable PU.1, which in turn alters the expression of many other genes that cause leukaemia. We have developed new AML models allowing reversible inhibition of PU.1, and have shown that re-engaging PU.1 function causes AML regression. This project aims to understand PU.1 functions in AML and identify rational drug targets for treatment-resistant disease.
Translating Advances In Molecular Oncology Into Improved Care For Patients With Haematological Malignancies
Funder
National Health and Medical Research Council
Funding Amount
$411,327.00
Summary
The purpose of my research is to develop and integrate into routine practice better treatment paradigms for patients with blood cancers – leukaemias, lymphomas, myeloma. My research seeks to (i) bring a new class of anti-cancer targeted therapy, inhibitors of Bcl-2, into routine care; (ii) discover the genetic changes that explain why slow growing lymphoid cancers change into rapidly fatal lymphomas; and (iii) integrate new molecular tests into the management of patients with acute leukaemia.
Myeloproliferative diseases (MPD) and leukemias arise from blood cells with faulty molecular signalling caused by genetic mutations. We are studying MPD and leukemias that carry over-active versions of the JAK2 signalling molecule. We will use human and mouse leukemias and MPD to discover how these diseases develop, and how we can use specific medications to stop these processes. Our goal is to discover new, improved ways to treat leukemias and MPDs.
Targeting Epigenetic Enzymes In Core Binding Factor AML
Funder
National Health and Medical Research Council
Funding Amount
$542,273.00
Summary
Acute myeloid leukemia (AML) is a devastating disease and there are ~900 new cases diagnosed annually in Australia. A subset of AML, called core binding factor (CBF) AML is more responsive to conventional chemotherapies than other AMLs however patients still relapse indicating a need for new therapies. We will use preclinical models of CBF AML to identify the proteins and pathways that these leukemias are “addicted” to in order to develop new treatment options for these patients.
Chronic Myeloid Leukaemia: Changing The Treatment Paradigm
Funder
National Health and Medical Research Council
Funding Amount
$1,162,778.00
Summary
Most patients with chronic myeloid leukaemia achieve excellent responses to therapy but need therapy for life. We have pioneered the concept that some patients can cease their therapy and not relapse (treatment free remission –TFR). By studying the immune system and the leukaemic stem cells we will determine why TFR is possible for some, but not all patients. This holds the key to improving the rate of TFR, thus moving the CML goal from disease control to cure.
I lead a research program to improve outcomes for patients with chronic myeloid leukaemia (CML). We aim to identify poor risk patients and test new treatment strategies to reduce adverse outcomes. In good risk patients we aim to reduce the need for lifelong drug dependency. Through a combination of clinical trials, innovative correlative studies, and strong scientific collaborations, my team will continue to improve outcomes for CML patients globally.
Molecular Understanding Of Combination Epigenetic Therapy In MLL-fusion Leukaemia
Funder
National Health and Medical Research Council
Funding Amount
$624,660.00
Summary
The poor prognosis conferred by chromosome breaks involving the MLL gene in acute leukaemia has not significantly changed in over twenty years. This fact highlights the urgent need to identify and develop novel therapeutic agents for this disease. This project will aim to understand the mechanisms leading to the initiation and maintenance of this aggressive disease. We will then use these insights to develop a rational combination of therapeutic agents.
EphA3, A Novel Target For Leukaemia Stem Cell Therapy
Funder
National Health and Medical Research Council
Funding Amount
$616,992.00
Summary
Patients with acute myeloid leukaemia often respond to therapy, but many relapse due to “leukemic stem cells” (LSC), the few cells in the original leukaemia which survive therapy. We focus on a protein (EphA3) which sits on LSCs and helps them interact with their environment. Disrupting this interaction may make these cells vulnerable to therapy. We aim to determine the function of EphA3 on LSCs and optimise the therapeutic use of an antibody against EphA3 which is currently in clinical trial.
Targeting Sphingosine Kinase 1 To Sensitise Acute Myeloid Leukaemia To BH3 Mimetic Therapy
Funder
National Health and Medical Research Council
Funding Amount
$670,005.00
Summary
Acute Myeloid Leukaemia (AML) patients are currently treated with chemotherapeutics and despite their success at achieving disease remission these responses are often short lived, resulting in relapse and death. We have identified sphingosine kinase 1 as a new drug target in AML. This proposal aims to examine the role of targeting sphingosine kinase 1 in combination with new targeted therapies in patient samples and preclinical mouse models of AML.