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Friday 18 January 2008

RAPID ROUNDUP: Cancer stem cells causing childhood leukaemia found – Australian experts respond

Research published today in Science confirms the existence of cancer stem cells as a cause of acute lymphoblastic leukaemia (ALL), the most common form of childhood cancer, supporting previous evidence that development of this childhood cancer begins in the womb. Australian experts comment on this research, and its implications for the progression and detection of the disease.

Feel free to use these quotes in your stories. If you wish to speak to one of these or another expert, contact the AusSMC on 08 8207 7415.



Professor Andrew Boyd is Head of the Leukaemia Foundation Laboratory at Queensland Institute of Medical Research, and is internationally recognised as a leader in haematological cancer research.

“This research adds a significant piece of data to the emerging concept that all tumours depend on the presence of a small population of highly proliferative tumour stem cells, a concept which originated from studies of acute myeloid leukaemia (AML). This has important implications for the development of new treatments, and in particular the idea that targeting these stem cells could cut the cancer off at its roots leading to a complete cure.

Hong and colleagues carefully analysed patients with a particular genetic change to the genetic material (TEL-AML1) which occurs in 1 in 4 cases of childhood acute lymphoma leukaemia (ALL). This article shows that the leukaemic process is maintained by a small population of leukaemic stem cells which closely resemble the normal blood stem cells for pre B cells, cells of the immune system which are the normal counterpart of ALL cells.

A second important observation was derived from the study of twins. One child had developed this form of ALL and her leukaemic cells had lost the normal TEL gene. When her healthy twins blood was examined a small population of cells with the TEL-AML1 abnormality was detected. These cells, however, retained a copy of the normal TEL gene and were clearly not leukaemic. This highlights the need for a sequence of critical genetic changes to turn a normal cell into a leukaemia but also shows that the TEL-AML1 abnormality is likely to be the first event in the sequence in this form of leukaemia.”



Professor John Rasko is Director of Cell and Molecular Therapies at the Sydney Cancer Centre, Royal Prince Alfred Hospital and Head of the Gene and Stem Cell Therapy Program at the Centenary Institute, University of Sydney.

"This interesting, if not revolutionary, study builds on our understanding of how leukaemia develops in the body. Although previous studies have demonstrated the concurrent appearance of diseases in twins, this study by an expert international consortium co-ordinated from the UK clearly demonstrates the multi-step requirements for childhood leukaemia to appear.

The results are also a very helpful in that they provide a glimpse of the timeframe during which a leukaemia may develop in the body from its earliest stages. One of the twins took two years to develop obvious leukaemia in her body, despite the fact that the earliest leukaemic precursor cells were present in her body at birth. This certainly tells us that years are required for the development of leukaemia. Indeed, another example that allows pinpointing of the exact time at which acute lymphoblastic leukaemia develops is in the context of gene therapy for severe immune disease. Despite the considerable clinical success achieved in treating severe immunodeficiency with experimental gene therapy, several children have developed a similar form of childhood leukaemia within two or three years following treatment. Exhaustive molecular testing has shown that the initiating event can be pinpointed to the time when the gene therapy was administered. So both this new study and previous gene therapy studies combined to tell us that childhood acute lymphoblastic leukaemia requires at least a couple of years to fully manifest itself.

These observations also offer the possibility that screening may be performed in the future to identify the earliest molecular signature for individuals possibly destined to develop serious diseases like leukaemia. No doubt the one twin who has not yet developed leukaemia, but has circulating precursor cells in her body, must be considered at some risk for the disease and will require vigilant clinical monitoring.”



Dr Linda Bendall is a Cancer Institute NSW Fellow at The University of Sydney.

"Within the cancer research field the concept that all cancer cells are not equal but that only a subset of cancer cells (often termed cancer stem cells) are capable of propagating the disease has become a hot topic for research. This concept is often linked to the idea that 'cancer stem cells' undergo the same or similar maturation processes as those observed in normal cells and that “cancer stem cells” originate from normal stem cells.

This paper clearly shows that for this particular type of acute lymphoblastic leukemia this is not the case, with the leukemia propagating cells having some 'stem cell' features, but clearly lacking others. Leukemia initiating cells identified in this paper share many features with the pre-leukemic cells that could also be found in the healthy identical twin of an infant with acute lymphoblastic leukemia. Although the pre-leukemic cells also display a maturation process, this differs from that of normal cells.

The identification and study of pre-leukemic cells permits an understanding of how the disease develops and results from this study suggests that pre-leukemic cells may be responsible for late relapse following treatment. Targeting pre-leukemic or leukemia initiating cells may be a way to eliminate late relapse of leukemia."