| Autor: |
Majeti R; Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University Medical Center, Stanford, California 94305, USA; email: irv@stanford.edu., Jamieson C; Sanford Stem Cell Clinical Center, University of California, San Diego, La Jolla, California 92093, USA., Pang WW; Jasper Therapeutics, Redwood City, California 94065, USA., Jaiswal S; Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA., Leeper NJ; Department of Surgery, Stanford University School of Medicine, Stanford, California 94305, USA., Wernig G; Department of Pathology, Stanford University School of Medicine, Stanford, California 94305, USA.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University Medical Center, Stanford, California 94305, USA; email: irv@stanford.edu., Weissman IL; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University Medical Center, Stanford, California 94305, USA; email: irv@stanford.edu. |
| Abstrakt: |
We proposed and demonstrated that myelogenous leukemia has a preleukemic phase. In the premalignant phase, normal hematopoietic stem cells (HSCs) gradually accumulate mutations leading to HSC clonal expansion, resulting in the emergence of leukemic stem cells (LSCs). Here, we show that preleukemic HSCs are the basis of clonal hematopoiesis, as well as late-onset blood diseases (chronic-phase chronic myeloid leukemia, myeloproliferative neoplasms, and myelodysplastic disease). The clones at some point each trigger surface expression of "eat me" signals for macrophages, and in the clones and their LSC progeny, this is countered by upregulation of "don't eat me" signals for macrophages such as CD47,opening the possibility of CD47-based therapies. We include evidence that similar processes result in fibroblast expansion in a variety of fibrotic diseases, and arterial smooth muscle clonal expansion is a basis of atherosclerosis, including upregulation of both "eat me" and "don't eat me" molecules on the pathogenic cells. |
