Haematology

Development & Research

Success in Training
Our high success rate in the Joint College Haematology training program continues with
Dr Daniel Thomas and Dr Pratyush Giri passing the Part I FRCPA and Dr Shir-Jing Ho passing the Part II.

Awards and Recognition
Professor Tim Hughes was promoted to Clinical Professor, University of Adelaide and was also awarded the 2006 Eric Susman Prize from the Royal Australasian College of Physicians for his original and groundbreaking research in chronic myeloid leukaemia (CML).  His contributions include defining the importance of molecular monitoring in CML patients receiving kinase inhibitor therapy, showing that the mutation profile helps clinicians to choose the best kinase inhibitor to use and using pre-therapy kinase sensitivity to tailor drug dose for each patients.  His work also led to a publication in the journal Nature describing the in-vivo kinetics of a human cancer.

Dr Peter Bardy was promoted to Associate Clinical Professor, University of Adelaide, and was appointed to the Medical Director, Division of Medicine, The Queen Elizabeth Hospital.

Mr Ken Davis of the Transfusion Medicine Unit was re-elected to be the President of the Australian Society of Blood Transfusion.

Staff Development
Deb White, PhD Student
Steven Blake, PhD Student
David Ross, PhD Student
Devendra Hiwase, PhD Student
Jane Engler, PhD Student
Nicola Hurst, PhD Student
Peter Casey, Master of Health Service Management.

Memberships of Committees and Service to Other Organizations

Second Preceptorship Program for Pan Pacific Haematologists in Chronic Myeloid Leukaemia
Professor Tim Hughes ran this program for the second year in a row.  This provides an opportunityto learn about the clinical management and laboratory monitoring of targeted therapy in chronic myeloid leukaemia. Over 40 haematologists and trainees came to Adelaide from countries in the Pan Pacific region for a 3.5 day course in the clinical and laboratory management of CML and related diseases. This preceptorship was run in partnership with Novartis. 

Committees:

• Sr Terry Ventrice
  Nurses Education Fund / Infection Control Committee /  NICS Pain Committee / Infusion Pump Committee / Oncology Course Advisory Committee / Transplant Nurses Assoc. (TNA) Conference Committee / Chemotherapy Competency working party / CPI Project ( blood product requirements in haematology ) / PICC Line Working Party/ Haematology Short Course
• Sr Lucy Hancock
• Occupational Health & Safety Committee / Haematology Short Course
  
• Sr Mel McMahon - Quality Committee
• Sr Kirsten Fellenberg
  TNA Education Committee / TNA Conference Committee
• Sr Trish Harris
  Haematology Short Course / Oncology Course Advisory (student rep)
• Mr Peter Casey
  Member oncology course advisory committee
  Clinical Title Holder, Dept Clinical Nursing, Adelaide University

Memberships:

• Professor Tim Hughes – Member (2006) and Chair (2007) of the NHMRC Grant
  Review Committee
• Transplant Nurses Association (TNA) -  Terry Ventrice , Jacqui Ruhl, Lucy
  Hancock, Eva Smyth, Trish Harris,  Jacqui Davis, Jane Opie, Amanda Catherwood, K. Fellenberg
• Cancer Nursing Society of Australia (CNSA)– Terry Ventrice, Jacqui Ruhl, Trish Harris, Eva Smyth, Lucy Hancock

Five Areas Of Divisional Research

1. Unlocking the keys to treatment efficacy in leukaemia
   While new treatment strategies, which specifically target the protein that causes chronic myeloid leukaemia, have been successful in the majority of patients, some patients do not respond well. The ability to predict these patients pre-treatment, will enable more effective “up front” management. Over the last year the IMVS has demonstrated that the efficacy of imatinib in inhibiting the action of the CML protein (BCR-ABL) is a key component of long term response. Furthermore, we have confirmed the protein involved in imatinib’s transport into CML cells, and more recently shown that it is the activity of this protein which is a key determinant of patient response.  Current studies are addressing the key transporters involved in the uptake of the second generation CML drugs, nilotinib and dasatinib. Using the approaches developed at the IMVS, patients can be pre-screened against all 3 drugs. This will allow for the establishment of a best response profile, and guide the choice of therapy for each individual CML patient. Furthermore the assays that have been developed are equally applicable to the cohort of patients who relapse on imatinib, providing a guide for the next most appropriate therapeutic choice. The increased knowledge in the key areas of mechanism of action, and intrinsic patient response, are significant in both a basic biology sense but also importantly, have the potential to significantly improve responses in some patients.



2. Identifying how cancers invade and destroy bone
   The research team has continued to focus its attention on identifying the molecular and cellular mechanisms behind why some cancers metastasise to, and destroy the skeleton. Specifically they are investigating the second most common haematological or blood cancer, termed multiple myeloma, which makes up approximately 1.4% of all cancers in South Australia.  Current best conventional therapy is non-curative, and the median survival time is currently 36 months. One of the most debilitating complications of this disease is the skeletal destruction which is seen in approximately 80% of all patients with multiple myeloma. The team have identified a number of potent factors that are associated with the skeletal destruction in myeloma, including the chemokine CXCL12 and its receptor CXCR4.  The identification of these factors may provide novel targets for future drug design.
   
   In addition, recent studies from the group have also demonstrated that the new leukaemia drug, Imatinib mesylate (Gleevec), currently used to treat patients with chronic myeloid leukaemia (CML) may be useful in treating the bone destruction in multiple myeloma and other cancers, by inhibiting cells responsible for the bone-destructive processes.  This was a previously unknown property of Imatinib mesylate and raises the possibility that it may be used to treat a variety of malignant and non-malignant diseases which involve bone loss, including cancer, osteoporosis and rheumatoid arthritis.



3. The use of mesenchymal precursor cells for regenerative medicine
   The IMVS in collaboration with Angioblast Systems Inc. New York, NY, USA and Mesoblast Ltd, Melbourne, Vic, have been developing mesenchymal stem cell based therapy in relation to cardiac, bone and cartilage tissue regeneration. Several new patents have been developed relating to the use of different MSC populations in multiple tissue engineering strategies to treat various cardiac and orthopaedic clinical problems. These patents, together with the initial 1999 MSC isolation patent have now been assigned to Angioblast Systems Inc. Our patent family was the basis for the formation of Angioblast’s sister company, Mesoblast Ltd., in order to further develop this technology for orthopaedic based clinical applications. This work has developed into several new collaborations with local experts in these fields.  More recently, Mesoblast Ltd. has secured a $2.7M AUS Industry grant specifically for developing MSC based strategies for the repair of cartilage tissues. These funds will be largely used for multiple pre-clinical ovine studies for intervertebral disk regeneration in an osteoarthritis model and for meniscus regeneration in an established meniscectomy model of early osteoarthritis.



4. Molecular regulation studies
   The two major interests of the Molecular Regulation laboratory are (i) the study of programmed cell death (apoptosis) of normal and cancer  cells and (ii) understanding the regulation of ion channels and transporters by ubiquitination. Apoptosis plays a fundamental role in cell and tissue homeostasis and its misregulation results in a variety of human diseases including many types of cancer. As apoptosis is a major mechanism for deleting harmful cells from the body, deciphering the mechanisms of apoptosis is essential for understanding disease process and to design effective treatment strategies for diseases which arise due to inappropriate apoptosis. Ubiquitin-mediated protein modification plays an essential role in cellular regulation during embryonic development, transcription and the cell cycle. Recent studies suggest that ubiquitination is a major regulator of many ion channels, receptors and transporters. The IMVS is studying the function of a group of ubiquitin-protein ligating enzymes (Nedd4-like proteins), which are key in defining substrate specificity of the ubiquitin system. A variety of molecular, cellular and gene knockout approaches are being used to study the physiological functions of these enzymes and establish their role in human diseases, such as haemochromatosis, anaemia and hypertension.



5. Identifying genes involved in leukaemia and blood development
   When the development of the cells of the human blood system goes wrong, the impact on an individual’s health can be dramatic. When the problem is caused by uncontrolled growth of blood cells, the consequence is often the disease called leukaemia. Many researchers have spent years listing and characterising specific rearrangements of chromosomes (the structures encoding the genes) that are associated with the enhanced growth of the leukaemia cells. These chromosome rearrangements provide visual clues that help identify the molecular regulators controlling blood development. Together with modern genetic manipulation techniques and animal models, IMVS researchers are hunting some of these regulators. They are close to identifying a previously unknown regulator of a type of blood cell called the megakaryocyte. Identification of such regulators is critical to increasing our understanding of how the blood system develops and how diseases such as leukaemia arise. Such research is also the first step to the development of novel therapeutics to treat such conditions.



6. Thrombosis / Haemostasis Research
   Based at the Frome Rd Campus, the Thrombosis and Haemostasis research program was recently formally established within the IMVS to build on a long history of previous research predominantly in the area of haemophilia. Current active areas of research focus on how laboratory tests impact on outcome in patients with bleeding and clotting disorders, and include; a) the role of global coagulation assays, such as the measurement of thrombin generation, in clinical practice, b) diagnostic testing for Heparin Induced Thrombocytopenia, c) the investigation of rare bleeding disorders; d) ongoing research into the relationship between genotype and laboratory parameters and clinical outcomes in patients with haemophilia. A thrombosis clinical trials program has also been established, with current active participation in national and international multicentre trials examining new ways of treating and diagnosing patients with thrombotic disorders.