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Haematopoietic stem cells and leukaemia

Leukaemia is a devastating blood cancer in which vast numbers of faulty white blood cells are made by the body. Leukaemia stem cells are responsible for producing these cancer cells and fuel the disease. Current therapies get rid of the bulk of the faulty white blood cells, but they do not destroy the leukaemia stem cells. Our research aims to understand the biology of leukaemia stem cells and identify tricks they use to escape treatments. We intend to harness this knowledge to devise new curative treatments that successfully target leukaemia stem cells. Since leukaemia serves as a paradigm for understanding other cancers, our work will also reveal clues on how to target other cancer stem cells.

Aims and areas of interest

Our laboratory employs multidisciplinary approaches to understand how haematopoietic stem cells (HSCs) chose to self-renew or differentiate and how these cell fate decisions are affected under pathological conditions to generate leukaemic stem cells. This knowledge is central to clinical applicability of stem cells and will be harnessed to achieve stem cell expansion for transplantation purposes and leukaemic stem cell eradication.

HSCs serve as a paradigm for understanding somatic stem cells, their immense clinical potential, and involvement in ageing and cancer formation. HSCs reside in niches within the bone marrow (BM) and sustain life-long haematopoiesis. HSCs are largely quiescent, undergo self-renewal, and generate progenitor cells, which differentiate to multiple blood lineages. The strict regulation of these fate decisions is essential for haematopoiesis and their dysregulation in haematopoietic stem and progenitor cells generates leukaemic stem cells, which drive blood cancer formation (i.e. leukaemogenesis) and are difficult to eradicate. Since current therapies often fail to eradicate LSCs it is of paramount importance to understand the mechanisms through which normal HSCs function and become transformed to cause leukaemias.

While HSCs reside in the hypoxic (low in oxygen) bone marrow microenvironment, the impact of hypoxia and hypoxia signalling pathways on normal HSC/progenitor fate decisions and leukaemogenesis remains largely unexplored. Our laboratory investigates the impact of hypoxia signalling pathways on HSC functions and addresses how these pathways are subverted to generate leukaemic stem cells. We hope to not only discover therapeutically targetable intrinsic characteristics of leukaemic stem cells, but also use leukaemic stem cells as a model to explore important mechanisms operating in other cancer stem cells.

Biography Prof Kranc

Prof Kranc obtained his medical degree in Poland (1994-2000) and pre-doctoral research training at the University of Oxford (1998-2000). He was awarded DPhil in Biochemistry from Lincoln College at the University of Oxford (2000-2003) where he held a Wellcome Prize PhD Studentship, Overseas Research Studentship and a Keith Murray Senior Scholarship. He obtained his postdoctoral training at the MRC Human Immunology Unit in Oxford (2003-2007). He was then a Junior Principal Investigator and a Beit Memorial Fellow at the MRC Molecular Haematology Unit at Oxford (2007-2010) and subsequently a Group Leader at the Paul O’Gorman Leukaemia Research Centre at the University of Glasgow (2010-2013). He joined the MRC Centre for Regenerative Medicine in 2013 as a CRUK Senior Fellow and Chair of Molecular Haematology. Prof Kranc is also a member of the Edinburgh Cancer Research Centre.

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