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Leukemia. 2014 Jan;28(1):34-43. doi: 10.1038/leu.2013.248. Epub 2013 Aug 27.

Clonal evolution in hematological malignancies and therapeutic implications.

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1] Cancer Vaccine Center, Dana-Farber Cancer Institute, Boston, MA, USA [2] Broad Institute, Cambridge, MA, USA [3] Department of Hematology, Yale Cancer Center, New Haven, CT, USA [4] Université Paris Diderot, Paris, France.
Broad Institute, Cambridge, MA, USA.
1] Broad Institute, Cambridge, MA, USA [2] Massachusetts General Hospital Cancer Center and Department of Pathology, Boston, MA, USA.
1] Cancer Vaccine Center, Dana-Farber Cancer Institute, Boston, MA, USA [2] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA [3] Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.


The ability of cancer to evolve and adapt is a principal challenge to therapy in general and to the paradigm of targeted therapy in particular. This ability is fueled by the co-existence of multiple, genetically heterogeneous subpopulations within the cancer cell population. Increasing evidence has supported the idea that these subpopulations are selected in a Darwinian fashion, by which the genetic landscape of the tumor is continuously reshaped. Massively parallel sequencing has enabled a recent surge in our ability to study this process, adding to previous efforts using cytogenetic methods and targeted sequencing. Altogether, these studies reveal the complex evolutionary trajectories occurring across individual hematological malignancies. They also suggest that while clonal evolution may contribute to resistance to therapy, treatment may also hasten the evolutionary process. New insights into this process challenge us to understand the impact of treatment on clonal evolution and inspire the development of novel prognostic and therapeutic strategies.

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