Leukaemia Foundation invests $3.9m+ in innovative ALL research
Better understanding and treating ALL is the focus of seven research projects that are part of the Leukaemia Foundation’s National Research Program.
This $3.99 million investment into ALL research at some of Australia’s leading research centres is aimed at developing better diagnostics, new therapeutics including precision medicine, clinical trials, a better understanding of ALL sub-types, decreasing treatment related side-effects, and improving quality of life.
Strategic Ecosystem Research Partnerships (SERP)
Of the Leukaemia Foundation’s nine current Strategic Ecosystem Research Partnership projects, three are focused on ALL.
One supports Professor Deb White’s research at the South Australian Health and Medical Research Institute (Adelaide). Her project, Precision Medicine in ALL, is looking at the recurrent gene fusions that characterise ALL; some of these gene fusions are known to confer high-risk and poor outcomes for patients. In this study, that runs until October 2022, people with newly diagnosed ALL will undergo genetic sequencing to identify their genetic fusions. The progression of ALL into the central nervous system will be examined and drugs will be tested to identify a panel of therapeutic agents for high-risk ALL. As well, the microbiomes of people who have survived an ALL diagnosis will be examined to add to understanding life-long effects.
The second ALL SERP project is a new blood cancer genomics clinical trial which will be headed by Professor Steven Lane at the Queensland Institute of Medical Research (Brisbane) and Professor Hamish Scott, University of South Australia, SA Genomics (Adelaide). Many patients with high-risk blood cancers relapse or fail to respond to therapy, and the outcomes for these patients are poor. The Blood Cancer Genomics Clinical Trial is a precision medicine pilot study using genomic screening to identify mutations in the cancer cell DNA; allowing for genetically directed targeted therapy for these high-risk patients who have failed therapy. This trial is in the final stages of development and is expected to start recruiting later this year.
Dr Daniel Gray’s lab at the Walter and Eliza Hall Institute of Medical Research (Melbourne) has identified a way to study how blood cancers develop resistance to therapy using a technology called mass cytometry CyTOF. This project, Deep profiling of ALL and myeloma for targeted therapies, will identify relevant disease pathways at the single-cell level for a better understanding of the mechanism by which blood cancer cells acquire treatment resistance and determining the impact of directed combination targeted therapy on treatment resistant blood cancer cell populations. The two-year deep profiling study, funded to August 2021, will analyse samples from patients taken before, during and after therapy. The aim is to apply the preliminary results observed in myeloma to ALL, which could lead to the design of better treatments and outcomes for these patients.
Our Translational Research Program (TRP) is co-funded with the Leukemia & Lymphoma Society (U.S.) and Snowdome Foundation, and two of the five current TRP projects are for ALL.
Dr Charles Mullighan, who established his research career in Adelaide, is now based at St Jude Children’s Research Hospital at Memphis in the U.S. His treatment focus is ALL and he received a TRP grant for his project, Improving therapy for CRLF2-rearranged Ph-like acute lymphoblastic leukaemia. This project is looking at a genetic mutation in an ALL sub-type called Ph-like ALL. This mutation leads to the expression of a gene called CRLF2. Patients with CRLF2-rearranged ALL can have poor outcomes as existing drugs show limited activity in treating this ALL sub-type which is why new therapeutics are urgently needed. The South Australian Health and Medical Research Institute (SAHMRI), where Dr Mullighan was previously a Cancer Theme Leader, is a collaborating institution on this three-year project that runs until July 2022.
The Leukaemia Foundation is helping the brightest medical and science graduates pursue a research career in blood cancer by collaborating with the Haematology Society of Australia and New Zealand (HSANZ) to co-fund PhD scholarships.
Over the last two years we have been proud to award six scholarships through our PhD Scholarship Program. Dr Wei Jiang, of the Westmead Cellular Therapies Group (Sydney), is one of our current PhD Scholarship recipients. Through her project, Clinical safety and efficacy of T-cell immunotherapies for infection and malignancy, Dr Jiang will participate in two clinical trials which could have a significant clinical benefit for patients who take part. One of the trials involves harnessing the power of a new type of engineered immune cell, called CAR-T (chimeric antigen receptor T-cells) and the other trial is looking at the use of pathogen-specific ‘smart’ T-cells in the treatment of resistant viral infections in patients who have had stem cell transplants.
Priority-driven collaborative research
The Leukaemia Foundation, though its National Research Program, supports the best emerging early career blood cancer researchers and clinicians through Cancer Australia’s Priority-driven Collaborative Cancer Research Scheme (PdCCR). Nurturing early career medical researchers and clinicians is critical to keeping the most promising and exciting talent in Australia. Over the last two years we have funded seven early career researchers through this scheme and two of these were in the field of ALL.
Preliminary work by Dr Michelle Henderson of the Children’s Cancer Institute (Sydney) led to the discovery of a new drug that has strong anti-leukaemia activity against even the most aggressive sub-types of leukaemia and now Dr Henderson is aiming to further develop this drug. Her research, Targeting the NAD pathway as a new therapeutic strategy for high-risk leukaemia in children, will develop the drug as a novel therapeutic strategy for aggressive leukaemia in children, to ultimately improve their survival and minimise the side-effects of treatment.
Another early career researcher funded through the PdCCR is Dr Laurence Cheung at the Telethon Kids Institute (Perth). His project, New therapeutic strategies for children with high-risk leukaemia by dissecting and targeting the bone marrow microenvironment, will address bone pain which affects many children diagnosed with leukaemia. Leukaemia cells can alter the surrounding bone cells and possibly favour leukaemia development in the bone marrow, and the immediate environment (neighbouring cells) of cancer cells influences many stages of cancer progression. This research will study the interaction between bone cells and leukaemia cells and evaluate if restoration to a healthy bone marrow environment improves treatment outcomes. Targeting both the cancer cells and the neighbouring cells has the potential to be a highly effective strategy to treat childhood leukaemia.Posted on March 17th, 2020
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