Convergent Epigenetic Evolution Drives Relapse in Acute Myeloid Leukemia.
| العنوان: | Convergent Epigenetic Evolution Drives Relapse in Acute Myeloid Leukemia. |
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| المؤلفون: | Nuno KA; Cancer Biology Graduate Program, Stanford University School of Medicine, Stanford, CA, USA.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.; Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.; These authors contributed to this work equally., Azizi A; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.; Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.; University of California Irvine School of Medicine, Irvine, California.; These authors contributed to this work equally., Köhnke T; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.; Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA., Lareau CA; Department of Pathology, Stanford University, Stanford, CA, USA.; Program in Immunology, Stanford University, Stanford, CA, USA., Ediwirickrema A; Cancer Biology Graduate Program, Stanford University School of Medicine, Stanford, CA, USA.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.; Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA., Ryan Corces M; Cancer Biology Graduate Program, Stanford University School of Medicine, Stanford, CA, USA.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.; Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.; Gladstone Institute of Neurological Disease, San Francisco, California.; Gladstone Institute of Data Science and Biotechnology, San Francisco, California.; Department of Neurology, University of California San Francisco, San Francisco, California., Satpathy AT; Department of Pathology, Stanford University, Stanford, CA, USA.; Program in Immunology, Stanford University, Stanford, CA, USA.; Parker Institute for Cancer Immunotherapy, Stanford University, Stanford, CA, USA.; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA., Majeti R; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.; Cancer Institute, Stanford University School of Medicine, Stanford, CA, USA.; Department of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA. |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2023 Oct 10. Date of Electronic Publication: 2023 Oct 10. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | Relapse of acute myeloid leukemia (AML) is highly aggressive and often treatment refractory. We analyzed previously published AML relapse cohorts and found that 40% of relapses occur without changes in driver mutations, suggesting that non-genetic mechanisms drive relapse in a large proportion of cases. We therefore characterized epigenetic patterns of AML relapse using 26 matched diagnosis-relapse samples with ATAC-seq. This analysis identified a relapse-specific chromatin accessibility signature for mutationally stable AML, suggesting that AML undergoes epigenetic evolution at relapse independent of mutational changes. Analysis of leukemia stem cell (LSC) chromatin changes at relapse indicated that this leukemic compartment underwent significantly less epigenetic evolution than non-LSCs, while epigenetic changes in non-LSCs reflected overall evolution of the bulk leukemia. Finally, we used single-cell ATAC-seq paired with mitochondrial sequencing (mtscATAC) to map clones from diagnosis into relapse along with their epigenetic features. We found that distinct mitochondrially-defined clones exhibit more similar chromatin accessibility at relapse relative to diagnosis, demonstrating convergent epigenetic evolution in relapsed AML. These results demonstrate that epigenetic evolution is a feature of relapsed AML and that convergent epigenetic evolution can occur following treatment with induction chemotherapy. Competing Interests: Declaration of Interests R.M. is on the Advisory Boards of Kodikaz Therapeutic Solutions, Orbital Therapeutics, and 858 Therapeutics and is an inventor on a number of patents related to CD47 cancer immunotherapy licensed to Gilead Sciences. R.M. is a co-founder and equity holder of Pheast Therapeutics, MyeloGene, and Orbital Therapeutics. A.T.S. is a founder of Immunai and Cartography Biosciences and receives research funding from Allogene Therapeutics and Merck Research Laboratories. C.A.L. is a consultant for Cartography Biosciences. |
| التعليقات: | Update in: Elife. 2024 Apr 22;13:. (PMID: 38647535) |
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| معلومات مُعتمدة: | K99 HG012579 United States HG NHGRI NIH HHS; R00 HG012579 United States HG NHGRI NIH HHS; R01 CA251331 United States CA NCI NIH HHS; UM1 HG012076 United States HG NHGRI NIH HHS |
| تواريخ الأحداث: | Date Created: 20231024 Latest Revision: 20240429 |
| رمز التحديث: | 20240429 |
| مُعرف محوري في PubMed: | PMC10592718 |
| DOI: | 10.1101/2023.10.10.561642 |
| PMID: | 37873452 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.1101/2023.10.10.561642 |
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