Genetic tracking identifies cancer stem cells in human patients
The gene mutations driving cancer have been tracked for the first time in patients back to a distinct set of cells at the root of cancer – cancer stem cells. The international research team, led by scientists at Karolinska Institutet and University of Oxford, studied a group of patients with myelodysplastic syndromes, a malignant blood condition which frequently develops into acute myeloid leukaemia.
The researchers say their findings, reported in the journal Cancer Cell, offer conclusive evidence for the existence of cancer stem cells. The concept of cancer stem cells has been a compelling but controversial idea for many years. It suggests that at the root of any cancer there is a small subset of cancer cells that are solely responsible for driving the growth and evolution of a patient’s cancer. These cancer stem cells replenish themselves and produce the other types of cancer cells, as normal stem cells produce other normal tissues.
The concept is important, because it suggests that only by developing treatments that get rid of the cancer stem cells will you be able to eradicate the cancer. Likewise, if you could selectively eliminate these cancer stem cells, the other remaining cancer cells would not be able to sustain the cancer. The existence of cancer stem cells has already been reported in a number of human cancers, but previous findings have remained controversial since the lab tests used to establish the identity of cancer stem cells have been shown to be unreliable and, in any case, do not reflect the “real situation” in an intact tumour in a patient.
Malignant cells in bone marrow
The researchers, led by Professor Sten Eirik W. Jacobsen at the MRC Weatherall Institute for Molecular Medicine in Oxford, and a guest professor at Karolinska Institutet, investigated malignant cells in the bone marrow of patients with myelodysplastic syndrome (MDS) and followed them over time. Using genetic tools to establish in which cells cancer-driving mutations originated and then propagated into other cancer cells, they demonstrated that a distinct and rare subset of MDS cells showed all the hallmarks of cancer stem cells, and that no other malignant MDS cells were able to propagate the tumour.
"I’m particularly excited since this publication more than anything is the result of successful collaborations between strong and complementary basic and clinical research environments at Oxford University and Karolinska Institutet, collaborations which are in the process of being further developed", comments Professor Jacobsen.
The study was funded by the Knut and Alice Wallenberg Foundation, the Leukemia and Lymphoma Society, Leukaemia and Lymphoma Research, and the National Institute of Health Research Oxford Biomedical Research Centre. Sten Eirik Jacobsen is a guest professor at the Department of Medicine, Huddinge, and the Department of Cell and Molecular Biology.
- Read more in a press release from the University of Oxford
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Publication
Myelodysplastic syndromes are propagated by rare and distinct human cancer stem cells in vivo
Petter S. Woll, Una Kjällquist, Onima Chowdhury, Helen Doolittle, David C.Wedge, Supat Thongjuea, Rikard Erlandsson, Mtakai Ngara, Kristina Anderson,Qiaolin Deng, Adam J. Mead, Laura Stenson, Alice Giustacchini, Sara Duarte, Eleni Giannoulatou, Stephen Taylor, Mohsen Karimi, Christian Scharenberg, Teresa Mortera-Blanco, Iain C. Macaulay, Sally-Ann Clark, Ingunn Dybedal, Dag Josefsen, Pierre Fenaux, Peter Hokland, Mette S Holm, Mario Cazzola, Luca Malcovati, Sudhir Tauro, David Bowen, Jacqueline Boultwood, Andrea Pellagatti, John E. Pimanda, Ashwin Unnikrishnan, Paresh Vyas, Gudrun Göhring, Brigitte Schlegelberger, Magnus Tobiasson, Gunnar Kvalheim, Stefan N. Constantinescu, Claus Nerlov, Lars Nilsson, Peter J. Campbell, Rickard Sandberg, Elli Papaemmanuil, Eva Hellström-Lindberg, Sten Linnarsson & Sten Eirik W. Jacobsen
Cancer Cell online 15 May 2014, doi: http://dx.doi.org/10.1016/j.ccr.2014.03.036