title: Pre-leukemic evolution of hematopoietic stem cells: the importance of early mutations in leukemogenesis.
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.
authors.affiliation: Program in Cancer Biology, Stanford Cancer Institute, Stanford Institute for Stem Cell Biology and Regenerative Medicine, Ludwig Center, Stanford, CA, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Corces-Zimmerman
authors.affiliation: 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.
authors.forename: R
authors.initials: R
authors.lastname: Majeti
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004195:Disease Models, Animal; D023281:Genomics; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007938:Leukemia / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000628:therapy; D051379:Mice; D009154:Mutation; D018365:Neoplasm, Residual / Q000175:diagnosis; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology