Contribution of Chronic Myeloid Leukaemia (CML) as a Disease Model to Define and Study Clonal Heterogeneity
Although tumour cell intra-clonal heterogeneity has been known for many years, its application in the oncology clinical practice (patient management, prognosis, etc.) remains limited. For this, chronic myeloid leukaemia (CML) is a remarkable model. Basic
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Contribution of Chronic Myeloid Leukaemia (CML) as a Disease Model to Define and Study Clonal Heterogeneity Marc G. Berger and Céline Bourgne
Abstract Although tumour cell intra-clonal heterogeneity has been known for many years, its application in the oncology clinical practice (patient management, prognosis, etc.) remains limited. For this, chronic myeloid leukaemia (CML) is a remarkable model. Basic research studies revealed the heterogeneity of the initial clone, and led to the hypothesis of the existence of leukemic stem cells. Nevertheless, the indisputable evidence of the intra-clonal heterogeneity role in the therapeutic response came from the outcomes of the treatment with tyrosine kinase inhibitors (the first targeted therapy in medicine) combined with the early and rigorous clinical and molecular monitoring of these patients. CML management already takes this heterogeneity into account for personalized patient follow-up. The adventure continues with the objectives of better tailoring the treatment and of curing the disease in most of the patients. Keywords Chronic myeloid leukaemia · Chronic phase · Leukaemia stem cell · Targeted therapy · Tyrosine kinase inhibitor · Intra-clonal heterogeneity · Precision medicine · Residual disease · Epigenetic · Single-cell transcriptome
M. G. Berger Université Clermont Auvergne, Equipe d’Accueil 7453 CHELTER, CHU Estaing, Clermont-Ferrand Cedex 1, France CHU Clermont-Ferrand, CHU Estaing, Hématologie Biologique, Clermont-Ferrand Cedex 1, France CHU Clermont-Ferrand, CHU Estaing, Hématologie Clinique, Clermont-Ferrand Cedex 1, France C. Bourgne (*) Université Clermont Auvergne, Equipe d’Accueil 7453 CHELTER, CHU Estaing, Clermont-Ferrand Cedex 1, France CHU Clermont-Ferrand, CHU Estaing, Hématologie Biologique, Clermont-Ferrand Cedex 1, France e-mail: [email protected] © Springer Nature Switzerland AG 2019 A. Birbrair (ed.), Stem Cells Heterogeneity in Cancer, Advances in Experimental Medicine and Biology 1139, https://doi.org/10.1007/978-3-030-14366-4_10
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M. G. Berger and C. Bourgne
10.1 Introduction Intra-clonal heterogeneity is a concept proposed by J. Dick’s group in the 1990s, following the identification of a sub-population of cells that can initiate acute myeloid leukaemia after grafting in non-obese diabetic mice with severe combined immunodeficiency disease (NOD/SCID) (Bonnet and Dick 1997; Lapidot et al. 1994). However, the transfer of this concept to the oncology clinical practice remains limited. In this sense, chronic myeloid leukaemia (CML) is a remarkable model. In most patients, CML is detected at the stage of chronic haematopathy with preservation of the differentiation capacity, and it always progresses to acute leukaemia after 4–6 years. This review focuses on the chronic phase of CML, before the progression to acute leukaemia, and summarizes the importance of the concept of intra-clonal heterogeneity in patient management in the era of targeted therapies and personalized treatments.
10.2 Chronic Myeloid Leukaemia 1
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