Leukaemia

Introduction

Blood is a complex tissue made up of red and white blood cells that are essential for many normal functions of an organism (e.g. oxygen supply, fighting infections, wound healing, blood clotting). Life-long production of all blood cells is maintained by a small number of blood stem cells that reside in the bone marrow. Blood formation is a step-wise and tightly controlled process during which blood stem cells first give rise to different immature blood cells that eventually produce all mature blood cells. Under pathological conditions, blood stem cells or immature cells slip out of control and become cancer stem cell that give rise to blood cancers.

Leukaemia is classically categorised into acute and chronic disease types depending on how fast it develops and progresses. Acute leukaemia is marked by a rapid increase in the number of immature white blood cells, which means that the blood and eventually other organs are being “overrun” by rogue immature leukaemic cells. Generally, chronic leukaemias are long-term conditions that develop slowly and affect more mature cells.  Both acute and chronic leukaemias can then be further classified depending on which cell type of the blood is affected, i.e. myeloid cells (which become platelets and immune cells) or lymphoid cells (which become immune cells).  In all cases, proper function of the immune and blood system is disrupted: a lack of mature platelets affects the clotting process, and early symptoms of the disease include easy bruising and excessive bleeding. Similarly, a lack of mature immune cells means that the body’s defence against infections is compromised, and cold and flu symptoms are frequently observed.

Some leukaemias are more difficult to treat than others and all types of leukaemias require very specific treatments. Acute leukaemia needs immediate treatment to prevent the cancer from affecting other organs, which happens when large numbers of cells are produced in a very short space of time and are spread by the blood stream; this is mostly done by resetting the bone marrow with a number of courses of chemotherapy and in many cases is followed by stem cell transplantation. Chronic leukaemia, in contrast, is often monitored for a certain period before deciding on a treatment course. However, in some cases during the course of chronic leukaemia, the disease can enter a phase where it suddenly begins to develop rapidly, which requires immediate treatments.

Work at CRM

• Prof Kamil Kranc and his team aim to understand how blood stem cells produce mature blood cells and how these processes are disrupted, creating ‘cancer stem cells’ which cause leukaemias. These cancer stem cells divide extremely rapildy and are very difficult to eliminate with currently available treatments. Therefore, in order to develop curative therapies that eliminate cancer stem cells in their entirety it is essential to understand how these rogue cells are made and how they cause leukaemia.  Prof Kranc hopes that by identifying important genes and external factors that affect the cells, we will be able to find drugs that specifically target and eliminate cancer stem cells. Furthermore, he expects that this knowledge will also contribute to finding new therapies for other cancers.

• Prof Alexander Medvinsky works on the development of haematopoietic stem cells (HSCs). Together with his team, he investigates how HSCs develop in the embryo and how the composition of their surrounding environment affects them. By identifying individual components, he has developed a technology to grow these cells in a dish and analyse how they interact with each other. This work will aid in the generation of HSCs from embryonic stem cells, which can then be used for clinical transplants that are commonly used to treat blood cancers and many other diseases.

• Complementing the work of Professors Medvinsky and Kranc, Prof Lesley Forrester also works on the generation of blood cell lineages from embryonic stem cells. One of her aims is to find a reliable technology to turn HSCs into immune cells (macrophages) and red blood cells. In the long-term, this knowledge will contribute to the manufacturing of cultured blood, which can be used in a therapeutic setting, and has the potential to make clinics independent of blood donations.

• Prof Clare Blackburn and her team have focused their work on the thymus, the organ that produces immune cells. Having identified the stem cells that are responsible for thymus formation in the developing embryo, she now aims to develop technologies to produce these cells in a dish. This is of particular interest with regards to the treatment of leukaemia, as the resetting of the immune system by chemotherapy is dependent on thymus activity and its provision of healthy immune cells.

• Dr Katrin Ottersbach studies a type of infant leukaemia with a particularly poor prognosis that is known to arise before birth. By looking at the prenatal development of the blood system her group aims to identify and study the target cell in which the presence of the mutation causes changes in cell behaviour that lead to the development of leukaemia. More information about the target cell may result in more effective treatments of this disease.

Frequently Asked Questions - Prof Kamil Kranc

1. Is the Centre involved in clinical trials?

   No, research at the MRC Centre for Regenerative Medicine is currently focused on further understanding of the development of leukaemia and other blood disorders. We are searching for new ways to target leukaemia and we hope to take part in future trials. At that stage we will provide information on this page about trials.

2. Can I take part in a future clinical trial? 

   Should the labs take part in future clinical trials, patients will be recruited locally through the UK’s National Health System (NHS).

3. Can you give me medical advice? 

   Unfortunately, for legal reasons, Prof Kamil Kranc and his team cannot give medical advice or recommend on a specific stem cell therapy or trial. We do recommend you take advice of your local healthcare team.

4. Where can I get more information? 

   Leukaemia: The charities CancerResearchUK and BloodWise provide support, advice and up-to-date information.

   Blood (cord) donation: Leukaemia patients need regular blood transfusions as part of their treatment. The NHS website provides detailed information how you can donate red blood cells, platelets and cord blood.

   Blood and cord blood stem cells: The www.eurostemcell.org website has two very helpful factsheets: blood stem cells, the pioneers of stem cell research and cord blood stem cells, current uses and future challenges 

   Stem cells and clinical trials: please see the Patients section on our website and follow the links.

5. I have Acute Myeloid Leukaemia (AML) and read about the research you published in the Journal of Experimental Medicine. Should I stop my treatment? 

   No, you should not stop your treatment. Please talk to your medical specialist if you have any queries about your treatment. There are many subtypes of AML. The study was specifically designed to understand the role of two molecules, Hif-1alpha and Hif-2alpha, in one particular type of leukaemia: AML caused by MLL translocations. The results indicated that future therapies designed to block these two molecules have no impact or may even worsen disease.

6. What is the impact of your recent JEM paper for patients with AML? 

   See also question five. The study has given us a greater understanding of the complexity of AML. Research will now focus on further understanding the role of the two molecules Hif-1alpha and Hif-2alpha and if the results are applicable to a wider range of blood cancers. Our study suggests the need for more tailored treatments, there might not be a ‘one size fits all’.

7. I would like to help. Can I donate my blood / bone marrow for research within your laboratory?

   Yes, you can help, see also question four on how to donate red blood cells, platelets and cord blood. When researchers at the Centre need live human tissue or blood samples for their research, they work closely with clinical haematologists in the UK and abroad. With consent of patients (and if our research has met all other requirements set by regulatory bodies), the haematologists kindly arrange this for us when we need samples.

8. If I can’t take part in a clinical trial or donate blood, can I help in other ways?

   Yes. Philanthropy in research is increasingly important as funding streams change. It is thanks to people like you that we are able to attract the brightest minds and provide world-class research facilities. If you wish to support our research efforts to better understand leukaemia and other blood disorders, you can help fundraise for CRM. As part of the online form you can specify that your funds are directly for supporting research into leukaemia. Your contribution and support is much appreciated.