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Responses to Tumour initiating factors and Regulation of Normal and Malignant Haematopoiesis The haematopoietic stem cell (HSC) resides within a specific environment enabling it to retain its self-renewal capacity or quiescent state. It is proposed that the HSC niche is hypoxic, a milieu within which the HSC is protected from intrinsic and extrinsic stimuli. We have investigated the haematopoietic phenotype of an HSC in a mouse model where hypoxia-regulated Vegfa expression is abrogated. In Vegfaδ/δ mice, the HRE in the Vegfa promoter has been deleted at both alleles, thereby inhibiting HIF-binding and subsequent activation of Vegfa expression following hypoxia. We show that hypoxic regulation of Vegfa expression within the haematopoietic system affects haematopoietic differentiation and numbers of HSCs to a small extent. Interestingly, Vegfa expression was shown to be reduced in highly purified HSCs from bone marrow of Vegfaδ/δ mice but not in mature cells, suggesting that the niche of the HSC is hypoxic. Acute lymphoblastic leukaemia (ALL) is the most common malignancy among children. Contemporary treatment protocols result in cure rates of 80-85 % but 15-20 % of children still experience relapse. A group of patient