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Abnormal production and function of blood cells underlies many human diseases.
Our haematology research seeks to understand blood cell formation and function in health and disease in order to develop better treatments for blood disorders.
Haematology research at the institute
Our haematology researchers:
- Define molecules controlling blood cell development and function.
- Identify how blood cell abnormalities lead to diseases such as leukaemia, lymphoma, myeloproliferative disorders and myelodysplasia.
- Identify new strategies to treat blood diseases.
What is haematology?
Haematology is the study of blood and blood cell production and function in health and disease.
Healthy blood is composed of blood cells and the plasma (liquid) in which they circulate. There are three main cellular components of blood:
- Red cells, which carry oxygen and are the most numerous cells in blood.
- Platelets, tiny cells that coordinate the control of bleeding
- White cells, which fight infections.
Nearly half the volume of our blood is made of blood cells with the rest being plasma.
Plasma is the solution that carries our blood cells around our body. Dissolved proteins in plasma also have many important functions. These include:
- Maintaining the right amount of water in our blood, by preventing it from leaking out of our blood vessels.
- Fighting infection (through immune proteins called antibodies).
- Binding and carrying nutrients to cells and removing waste products.
- Carrying signals (hormones) around the body.
- Allowing blood clots to form in close collaboration with blood platelets when bleeding occurs.
Defects in blood cells or plasma proteins can be associated with many human diseases.
How are blood cells formed?
In an adult, blood cells are produced by stem cells in the bone marrow. One blood stem cell can produce all the blood cells in our system.
Progenitor cells develop from stem cells. They expand and mature, becoming much more specialised in their functions while becoming limited in the types of mature blood cells they produce. The two main types of progenitor cells are:
- Lymphoid progenitor cells, which develop into white blood cells called lymphocytes and other cells involved in the adaptive (specialised) immune system.
- Myeloid progenitor cells, which develop into non-lymphocyte white blood cells such as neutrophils, as well as red blood cells, and megakaryocytes (which form platelets).
All blood cells start with the same genetic code (genome), but as the cells develop, different genes switch on and off. This highly regulated process controls the protein machinery a blood cell makes and, ultimately, how a blood cell behaves and functions.
This highly regulated switching on and off of specific blood cell genes explains how different blood cells have vastly different functions within the body.
Our researchers have identified a detailed ‘road map’ of gene expression in blood cells which maps out which genes are turned on or off at every stage of blood cell development.
Colony stimulating factors
The growth, survival and function of blood cells are critically controlled by proteins, called cytokines, that are dissolved in the plasma. A large number of cytokines regulate a cell’s decision to become one blood cell type or another. Cytokines also regulate cells’ responses to emergencies such as bleeding or infection.
One particularly important class of cytokines involved in blood cell development is the colony stimulating factors. Colony stimulating factors (CSFs) were discovered at the Walter and Eliza Hall Institute by Professor Donald Metcalf in collaboration with Dr Ray Bradley from The University of Melbourne.
Colony stimulating factors have many functions including:
- Directing blood progenitors to form different types of white blood cells.
- Instructing blood cells to divide
- Regulating white blood cell function.
Colony stimulating factors are now used routinely to treat patients undergoing chemotherapy or in bone marrow transplantation.
Diseases of the blood
Abnormal blood cell production or function can cause many diseases. Understanding how these occur can lead to new strategies for treatment of these diseases.
Blood cell deficiencies
If too few blood cells are produced or excessive blood cells are lost, such as through bleeding, problems arise from the resultant blood cell deficiencies. These include:
- Anaemia, where too few red blood cells leads to problems such as tiredness, lethargy and blood circulation problems.
- Leukopenia, where too few white cells leads to immunodeficiency, increasing the risk of infection.
- Thrombocytopenia, where having too few platelets increases the risk of bleeding.
Blood cell cancers
The production of too many blood cells or uncontrolled growth of abnormal blood cells is the basis of blood cancers.
- Leukaemias are diseases in which an abnormal number of immature blood cells are produced in the bone marrow and can be detected circulating in the blood.
- Lymphomas are diseases in which abnormal lymphocytes grow, causing swelling of lymphocyte-containing tissues such as the lymph nodes or spleen.
- Myeloproliferative diseases, a range of conditions in which too many mature blood cells are produced. This leads to problems with blood circulation, and an increased risk of developing an aggressive leukaemia.
Blood clotting problems
Bleeding occurs when there is a breach of a blood vessel. Blood clotting is the important response creating a clot that plugs the wound to stop the blood vessel from bleeding. Clots are composed of:
- Platelets, which initiate and coordinate blood clotting.
- Clotting factors, which are soluble proteins in the blood that are converted into an ‘insoluble’ fibrin mesh to stabilise a blood clot.
Within a clot, platelets are critical for sending signals and triggering clot formation and wound repair. Some of these signals may also attract immune cells to the injured area, and instruct them to be ready to fight potential infection.
Several diseases are associated with problems of platelets or clotting factors.
Deficiencies or abnormalities in the function of platelets or clotting factors can lead to excessive bleeding. Examples of this include:
- Thrombocytopaenia, meaning a lack of platelets, can predispose to excessive bleeding.
- Haemophilia, in which a particular clotting factor is not produced, impeding clot formation.
Excessive numbers of platelets or an imbalance of clotting and anti-clotting factors can cause blood clots to form and block blood vessels to critical organs.
Some diseases that involve problems with blood clotting include:
- Essential thrombocythemia, a myeloproliferative disease, in which too many platelets are produced, causing a tendency to excessive clotting.
- Thrombophilia, in which an imbalance of clotting and anti-clotting proteins creates a predisposition to clot formation.
- Stroke, in which a blood clot can block the blood supply to the brain.
- Acute myocardial infarction (heart attack), in which a blood clot blocks supply to a heart blood vessel.
Blood donation and blood stem cell transplantation
Several blood cell deficiencies (such as anaemia, thrombocytopenia, and, occasionally, leukopenia) and blood clotting disorders (such as haemophilia) can be treated by replacing the missing blood component.
In all situations requiring blood cell replacement, the missing blood component comes from healthy volunteer donors. Missing plasma protein components can also be replaced by plasma from healthy volunteer donors. Recently genetic technology has been used to produce particular blood proteins.
In circumstances where a patient’s bone marrow stem cells need to be replaced, a specialised medical procedure called a bone marrow transplant can be undertaken. This replaces the bone marrow of the patient (bone marrow transplant recipient) with the stem cells that had been previously collected from the patient, or from a volunteer donor (bone marrow donor).
Haematologists are doctors who specialise in blood disorders and blood disease therapy.