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Blood, 1 March 2005, Vol. 105, No. 5, pp. 1862-1866. Prepublished online as a Blood First Edition Paper on November 4, 2004; DOI 10.1182/blood-2004-08-3373. This Article Full Text (PDF) All Versions of this Article: 2004-08-3373v1 105/5/1862    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Elrick, L. J Articles by Holyoake, T. L Search for Related Content PubMed PubMed Citation Articles by Elrick, L. J Articles by Holyoake, T. L Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 1, 2004 Accepted October 27, 2004 Punish the parent not the progeny Lucy J Elrick, Heather G Jorgensen, Joanne C Mountford, and Tessa L Holyoake* Section of Experimental Haematology, Division of Cancer Sciences & Molecular Pathology, University of Glasgow, Glasgow, UK * Corresponding author; email: tlh1g{at}clinmed.gla.ac.uk. Chronic myeloid leukaemia (CML) is sustained by a rare population of primitive, quiescent, BCR-ABL+ cells and represents an excellent example of a malignancy in which tumour initiating cells represent the key to disease eradication. CML is also the first malignancy for which targeted therapy has replaced conventional chemotherapy. Within a vast excess of proliferating progenitor cells that express BCR-ABL and are exquisitely sensitive to the tyrosine kinase inhibitor imatinib mesylate (IM), resides a small population of quiescent leukaemic cells that, despite higher levels of BCR-ABL transcripts, exhibits innate insensitivity to IM. These cells remain after IM therapy, even when apparently complete responses are achieved, and probably explain molecular disease persistence. Although it can be argued that patients may survive for many years with low levels of leukaemia still present, it is possible to achieve disease clearance at the molecular level following an allogeneic stem cell transplant. The emergence of drug resistance with IM monotherapy also argues in favour of complete disease eradication that we believe should remain the ultimate therapeutic goal in CML. New approaches to the elimination of these primitive CML cells may thus be crucial to the development of curative strategies. 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