Arrow grant helps in developing new therapies and diagnostic tests

February 12, 2018
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Written by Dr. Tim Molloy (senior researcher)

The Blood, Stem Cell, and Cancer Research (BSSCR) laboratory is a multidisciplinary research group consisting of clinicians, postdoctoral scientists, and students situated within the Department of Haematology and Bone Marrow Transplantation of St Vincent’s Hospital. Arrow has generously been supporting some of our key research lines for many years. One of these is centred around optimising bone marrow transplantation for the treatment of Acute Myeloid Leukaemia (AML), in which we are aiming to develop new diagnostic tests to guide transplant timing and also couple it with novel complementary therapeutic strategies.

AML is a blood cancer caused by the accumulation of specific mutations in one or more ‘stem’ cells that make up the haematopoietic system.  These then give rise to huge numbers of daughter ‘myeloid’ cells in an uncontrolled manner which accumulate in the blood and bone marrow, eventually crowding out important healthy cells such as white and red cells. This leads to various serious symptoms in affected individuals, and for many patients is unfortunately fatal. Those over the age of 60 are particularly affected by the disease having both higher incidence and mortality, so given Australia’s ageing population AML’s already significant health and economic burden is predicted to only increase in future.

What is interesting, however, is that while overall outcomes are generally poor for many patients, AMl is actually quite a clinically heterogenous disease – while some patients will unfortunately experience relapse despite quite aggressive therapy, others have an excellent response to treatment leading to lasting remission and cure. This is important because despite this large variation in patient response to treatment, therapy for almost all AML patients has remained largely unchanged over the last four decades. We therefore have a major research focus on developing new diagnostic tests and treatment strategies for this disease, so we can better tailor treatments for individual patients with the hope of eventually significantly increasing the cure rate.

Around five years ago, Arrow provided some seed funding to support a new postdoctoral scientist and some key equipment for our lab. This donation allowed us to pursue a new pilot research project into AML that aimed to compare the DNA of patients who responded well to therapy to those that didn’t. This work led to the identification of a gene called “microRNA-10a”, which appeared to be switched on specifically in the leukaemic cells of patients who responded poorly to therapy. Compared to normal healthy bone marrow, we found it to be at levels at least 80-fold higher in these poor prognosis patients which led us to hypothesize that it may be important for the biology of these leukaemic cells. Our findings attracted the interest of members of one of Europe’s largest leukaemia clinical trials groups, the Study Alliance Leukaemia (SAL), who were able to provide a valuable set of AML specimens from patients enrolled into one of their large trials that wanted to determine the optimal timing of bone marrow transplantation during treatment.

We hypothesized that by measuring microRNA-10a we could identify at diagnosis which patients were likely to be high-risk and should therefore receive more aggressive treatment, including early bone marrow transplantation, rather than waiting until later in their treatment as is normally done. The key finding of our study was that in the patient samples we analysed, those that were low in microRNA-10a strongly benefitted from early bone marrow transplantation – in fact these patients had a 90% survival rate compared to less than 30% of those with high microRNA-10a.

This early data therefore suggests that microRNA-10a could form the basis of a valuable clinical test able inform a clinician about the optimal timing of bone marrow transplantation, and we are currently further validating these important findings with additional patient samples. Seed funding for this project from Arrow was vital to get it to where it is today, and our team and collaborators are extremely grateful for their continuing support.

 

Researchers: Thanh Vu, Kristy Wang, Helen Tao, Tim Molloy, and David Ma.

Department of Haematology, and Blood, Stem Cell and Cancer Research Program

St Vincent’s Hospital Center for Applied Medical Research

St Vincent’s Hospital Sydney