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Clonal evolution in leukemia
Nature Medicinevolume 23, pages1135–1145 (2017)Cite this article
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Abstract
Human leukemias are liquid malignancies characterized by diffuse infiltration of the bone marrow by transformed hematopoietic progenitors. The accessibility of tumor cells obtained from peripheral blood or through bone marrow aspirates, together with recent advances in cancer genomics and single-cell molecular analysis, have facilitated the study of clonal populations and their genetic and epigenetic evolution over time with unprecedented detail. The results of these analyses challenge the classic view of leukemia as a clonal homogeneous diffuse tumor and introduce a more complex and dynamic scenario. In this review, we present current concepts on the role of clonal evolution in lymphoid and myeloid leukemia as a driver of tumor initiation, disease progression and relapse. We also discuss the implications of these concepts in our understanding of the evolutionary mechanisms involved in leukemia transformation and therapy resistance.
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Acknowledgements
We thank M. Mittelbrunn (CBM-Hospital 12 de Octubre, Madrid, Spain), X.S. Puente (Universidad de Oviedo, Oviedo, Spain), P. Menéndez (J. Carreras Leukemia Research Institute, Barcelona, Spain), R. Rabadán (Columbia University, New York, New York, USA), J. Soulier (Université Paris Diderot, Paris, France) and all members of our labs for their helpful comments on the manuscript. A.A.F. is supported by grants from the National Cancer Institute (NCI) of the National Institutes of Health (NIH), the Leukemia & Lymphoma Society, the Chemotherapy Foundation and the Rally Foundation. C.L.-O. is supported by grants from European Union (DeAge, ERC-Advanced Grant), Ministerio de Economía y Competitividad SAF2014-52413-R, Instituto de Salud Carlos III (RTICC), CIBERONC, Plan Feder, and EDP Foundation. The generous support by J.I. Cabrera is also acknowledged.
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Department of Pediatrics, Columbia University, New York, New York, USA
Adolfo A Ferrando
Department of Pathology and Cell Biology, Columbia University, New York, New York, USA
Adolfo A Ferrando
Institute for Cancer Genetics, Columbia University, New York, New York, USA
Adolfo A Ferrando
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología (IUOPA), Universidad de Oviedo, Oviedo, Spain
Carlos López-Otín
Centro de Investigación Biomédica en Red de Cáncer, Spain
Carlos López-Otín
- Adolfo A Ferrando
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- Carlos López-Otín
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Correspondence toAdolfo A Ferrando orCarlos López-Otín.
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Ferrando, A., López-Otín, C. Clonal evolution in leukemia.Nat Med23, 1135–1145 (2017). https://doi.org/10.1038/nm.4410
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