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Leukemia. 2014 Dec;28(12):2276-82. doi: 10.1038/leu.2014.211. Epub 2014 Jul 9.

Pre-leukemic evolution of hematopoietic stem cells: the importance of early mutations in leukemogenesis.

Author information

1
Program in Cancer Biology, Stanford Cancer Institute, Stanford Institute for Stem Cell Biology and Regenerative Medicine, Ludwig Center, Stanford, CA, USA.
2
1] Program in Cancer Biology, Stanford Cancer Institute, Stanford Institute for Stem Cell Biology and Regenerative Medicine, Ludwig Center, Stanford, CA, USA [2] Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Abstract

Cancer has been shown to result from the sequential acquisition of genetic alterations in a single lineage of cells. In leukemia, increasing evidence has supported the idea that this accumulation of mutations occurs in self-renewing hematopoietic stem cells (HSCs). These HSCs containing some, but not all, leukemia-specific mutations have been termed as pre-leukemic. Multiple recent studies have sought to understand these pre-leukemic HSCs and determine to what extent they contribute to leukemogenesis. These studies have elucidated patterns in mutation acquisition in leukemia, demonstrated resistance of pre-leukemic cells to standard induction chemotherapy and identified these pre-leukemic cells as a putative reservoir for the generation of relapsed disease. When combined with decades of research on clonal evolution in leukemia, mouse models of leukemogenesis, and recent massively parallel sequencing-based studies of primary patient leukemia, studies of pre-leukemic HSCs begin to piece together the evolutionary puzzle of leukemogenesis. These results have broad implications for leukemia treatment, targeted therapies, minimal residual disease monitoring and early detection screening.

PMID:
25005245
PMCID:
PMC4262622
DOI:
10.1038/leu.2014.211
[Indexed for MEDLINE]
Free PMC Article

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