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Are Leukaemic Stem Cells Restricted to a Single Cell Lineage?

1
School of Biomedical Sciences, Institute of Clinical Sciences, University of Birmingham, Birmingham B15 2TT, UK
2
School of Law, University of Salamanca, 37007 Salamanca, Spain
3
Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Moleculary Celular del Cáncer, CSIC/Universidad de Salamanca, 37007 Salamanca, Spain
4
Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(1), 45; https://doi.org/10.3390/ijms21010045
Received: 27 November 2019 / Accepted: 16 December 2019 / Published: 19 December 2019
(This article belongs to the Collection Feature Papers in Molecular Biology)
Cancer-stem-cell theory states that most, if not all, cancers arise from a stem/uncommitted cell. This theory revolutionised our view to reflect that cancer consists of a hierarchy of cells that mimic normal cell development. Elegant studies of twins who both developed acute lymphoblastic leukaemia in childhood revealed that at least two genomic insults are required for cancer to develop. These ‘hits’ do not appear to confer a growth advantage to cancer cells, nor do cancer cells appear to be better equipped to survive than normal cells. Cancer cells created by investigators by introducing specific genomic insults generally belong to one cell lineage. For example, transgenic mice in which the LIM-only 2 (LMO2, associated with human acute T-lymphoblastic leukaemia) and BCR-ABLp210 (associated with human chronic myeloid leukaemia) oncogenes were active solely within the haematopoietic stem-cell compartment developed T-lymphocyte and neutrophil lineage-restricted leukaemia, respectively. This recapitulated the human form of these diseases. This ‘hardwiring’ of lineage affiliation, either throughout leukaemic stem cell development or at a particular stage, is different to the behaviour of normal haematopoietic stem cells. While normal cells directly commit to a developmental pathway, they also remain versatile and can develop into a terminally differentiated cell that is not part of the initial lineage. Many cancer stem cells do not have this versatility, and this is an essential difference between normal and cancer stem cells. In this report, we review findings that support this notion. View Full-Text
Keywords: leukaemia; stem cells; haematopoiesis; lineage decision making; oncogenes; cancer leukaemia; stem cells; haematopoiesis; lineage decision making; oncogenes; cancer
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Brown, G.; Sánchez, L.; Sánchez-García, I. Are Leukaemic Stem Cells Restricted to a Single Cell Lineage? Int. J. Mol. Sci. 2020, 21, 45.

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