A metaphase cell positive for the bcr/abl rearrangement using FISH. The chromosomes can be seen in blue. The chromosome that is labeled with green and red spots (up left) is the one where the wrong rearrangement is present

Positive metaphase Bcr-Abl in CML highlighted by FISH

Recent discoveries about the role of stem cells in cancer have created new opportunities for cancer research. As scientists learn more of their cancer-initiating properties, stem cells are emerging as potential therapeutic targets for many types of cancers.

The existence of a small population of 'cancer-initiating cells'
responsible for tumour maintenance was originally demonstrated in
leukemia and the concept is also being tested in a variety of solid tumours. 

Leukemia-initiating cells, particularly those that are in the quiescent
state, are thought to be resistant to both chemotherapy and targeted
therapies, resulting in disease relapse.  Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder in which the
leukemia-initiating cell pool may not always be eradicated by current therapy,
leading to disease relapse on drug discontinuation.  Although relapse in CML is rare (<10-15% of cases), when it does occur the stem cells can replicate in significant numbers. 

More recently, the role of promyelocytic leukemia protein (PML) tumour
suppressor in hematopoietic stem cell maintenance has been examined.  A new
therapeutic approach for targeting quiescent leukemia-initiating cells
and possibly cancer-initiating cells by pharmacological inhibition of
PML may evolve.

Similarly, the role of quiescent stem cells in breast cancer has been reported, with small studies involving the targeted small molecule kinase inhibitor, lapatinib.  Other studies have noted a relationship between stem cells and patient outcomes in pancreatic, bladder, breast and glioma carcinomas, for example. 

Present chemotherapy options eliminate the bulk of the tumour but leave a core of these cancer stem cells with high capacity for repair and renewal.  Identifying the stem cells and designing new therapies is therefore a key focus in drug development for the near future.




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