M. Ryan Corces1, Wan‐Jen Hong2,3,1, Irving L. Weissman1, Bruno C. Medeiros3, Ravindra Majeti2,3,1
1Program in Cancer Biology, Ludwig Center, Cancer Institute, Institute for Stem Cell Biology and Regenerative Medicine, and
2Department of Medicine
3Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA 94305
Tóm tắt
Significance
A growing body of evidence has determined that somatic mutations in acute myeloid leukemia (AML) accumulate in self-renewing hematopoietic stem cells (HSCs). Thus, at the time of diagnosis, AML patients harbor preleukemic HSCs containing some, but not all, of the mutations in the downstream leukemia. Despite these findings, common patterns of preleukemic clonal evolution have not been determined, nor has the response of preleukemic HSCs to standard therapy been identified. This report addresses both of these questions determining that there are common patterns of preleukemic clonal evolution in AML, and that these preleukemic HSCs often survive standard induction chemotherapy. This study is of interest to the AML field, and broadly in cancer genomics as the principle that stem cells acquire initial cancer-initiating mutations is likely to extend beyond AML.
