Pre-leukemic hematopoietic stem cells are clonal antecedents of human acute myeloid leukemia
Abstract/Contents
- Abstract
- Cancer is a clonal disease in which multiple mutations are sequentially acquired. Little is known about the genetics of founding and early mutations in most forms of cancer, including acute myeloid leukemia (AML), because pre-cancerous cells are generally clinically silent and are outcompeted by their malignant descendants. We report the identification of a panel of cell surface markers that enable the prospective separation of rare, residual hematopoietic stem cells (HSC) from human AML patient samples. Subsequently, we used targeted exome sequencing to identify cancer-associated mutations in five leukemia genomes and, in two of these cases, identified a subset of mutations in patient-matched HSC. Through the genetic investigation of pre-leukemic HSC, we identify a clonal progression of multiple mutations in AML with relevance to design of targeted therapies. The existence of such pre-leukemic HSC reveals the clonal evolution of AML with HSC as the AML cell of origin, and identifies a potential mechanism behind relapse.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Copyright date | 2012 |
| Publication date | 2011, c2012; 2011 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Jan, Max |
|---|---|
| Associated with | Stanford University, Cancer Biology Program |
| Primary advisor | Majeti, Ravindra, 1972- |
| Primary advisor | Weissman, Irving L |
| Thesis advisor | Majeti, Ravindra, 1972- |
| Thesis advisor | Weissman, Irving L |
| Thesis advisor | Clarke, Michael F |
| Thesis advisor | Levy, Ronald, 1941 December 6- |
| Thesis advisor | Mitchell, Beverly S |
| Advisor | Clarke, Michael F |
| Advisor | Levy, Ronald, 1941 December 6- |
| Advisor | Mitchell, Beverly S |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Max Jan. |
|---|---|
| Note | Submitted to the Program in Cancer Biology. |
| Thesis | Ph. D. Stanford University 2012 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2011 by Max Jan
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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