Page 15

Leukaemia Stem Cell Biology Leukaemias and many other cancers have recently been demonstrated to be wholly dependent upon a small population of so -called cancer stem cells for their continued growth and propagation. These cells represent the most critical targets for treatment of leukaemia and a greater understanding of their biology and its interface with normal stem cell function is fundamental to improving treatment outcomes in leukaemia. The focus of the Huntly laboratory is on this interface between normal and malignant haematopoietic stem cell biology. We use a combination of techniques in cell line and animal models as well as confirmatory studies in primary human tissue to dissect stem cell function. Our group is complemented by a number of other local researchers within the Stem Cell Insitute with similar interests (Professors Green Gottgens and Warren and Dr Ottersbach). Our aim is to understand how normal stem cell stem cell function is subverted in cancer and how these processes might be therapeutically targeted to improve the outcome in haematological cancers, many of which have a dismal survival rate. A recent example of our work is the identification of the Bromodomain and extra terminal (BET) proteins as critical mediators of leukaemia stem cells in acute myeloid leukaemia (AML) and the development of an inhibitor of these proteins that is about to enter early phase clinical trials in relapsed blood cancers.

Brian Huntly Dr Brian Huntly is a clinical academic who combines running a laboratory group with his practice as a Consultant Haematologist in Addenbrookes Hopsital. He studied Medicine at Edinburgh, trained in Haematology in Dundee and Cambridge and is a member of the Royal College of Physicians and a Fellow of the Royal College of Pathologists. He studied for his PhD in Cambridge and performed post-doctoral work at Harvard, prior to returning to Cambridge to set up his own research group. .

Funding Inhibition of BET proteins switches off critical pathways in leukaemia stem cells. In the left panel, the MLL-AF4/AF9 leukaemia mutation is localized to DNA by the BET proteins Brd3 and 4, where it causes expression of drivers of leukaemia such as BCL2, C-MYC and CDK6. Inhibition of this localization with BET inhibitors (I-BET), switches off this the expression of these genes and causes the leukaemia to regress.

Leukaemia Lymphoma Research Wellcome Trust Kay Kendal Leukaemia Fund Leukemia Lymphoma society of America

Key Publications

Group Members

Dawson MA, Prinjha RK, Dittman A, Giotopoulos G, Bantscheff M, Chan WI, Robson SC, Chung C, Hopf C, Savitski MM, Huthmacher C, Gudgin E, Lugo D, Beinke S, Soden PE, Dรถhner K, Delwel R, Burnett AK, Auger KR, Mirguet O, Jeffrey P, Drewes G, Lee K, Huntly BJP *, Kouzarides T *. Displacement of BRD3/4 from chromatin as an effective treatment for MLL-fusion leukaemia Nature. 2011 Oct 2 *joint senior authors. PMID:21964340

George Giotopoulos Mark Dawson Sarah Putwain Sarah Horton Eshwar Meduri Paulo Gallipoli Faisal Basheer Chun Fong Jessica Morrison

Anand S, Stedham FE, Gudgin E, Beer PA, Bench AJ, Erber W, Green AR, Huntly BJP. The JAK2 V617F mutation alters myeloid ontogeny predominantly through effects outside of the hematopoietic stem and progenitor compartment. Blood. 2011 May 11. [Epub ahead of print] PMID:21562050 Kvinlaug BT, Chan WI, Bullinger L, Sears C, Paul D, Okabe R, Lee BH, Benner A, De Silva I, Valk P, Delwel R, Armstrong SA, Dรถhner H, Gilliland DG, Huntly BJP. Common and overlapping pathways contribute to the evolution of acute myeloid leukaemias. Cancer Res. 2011 Apr 19. [Epub ahead of print] PMID:21505102


Cambridge Stem Cell Institute Brochure 2012  
Cambridge Stem Cell Institute Brochure 2012