@article{4488b003cb8441ed883027612c57d733,
title = "Oncogenic gene expression and epigenetic remodeling of cis-regulatory elements in ASXL1-mutant chronic myelomonocytic leukemia",
abstract = "Myeloid neoplasms are clonal hematopoietic stem cell disorders driven by the sequential acquisition of recurrent genetic lesions. Truncating mutations in the chromatin remodeler ASXL1 (ASXL1MT) are associated with a high-risk disease phenotype with increased proliferation, epigenetic therapeutic resistance, and poor survival outcomes. We performed a multi-omics interrogation to define gene expression and chromatin remodeling associated with ASXL1MT in chronic myelomonocytic leukemia (CMML). ASXL1MT are associated with a loss of repressive histone methylation and increase in permissive histone methylation and acetylation in promoter regions. ASXL1MT are further associated with de novo accessibility of distal enhancers binding ETS transcription factors, targeting important leukemogenic driver genes. Chromatin remodeling of promoters and enhancers is strongly associated with gene expression and heterogenous among overexpressed genes. These results provide a comprehensive map of the transcriptome and chromatin landscape of ASXL1MT CMML, forming an important framework for the development of novel therapeutic strategies targeting oncogenic cis interactions.",
author = "Moritz Binder and Carr, {Ryan M.} and Lasho, {Terra L.} and Finke, {Christy M.} and Mangaonkar, {Abhishek A.} and Pin, {Christopher L.} and Berger, {Kurt R.} and Amelia Mazzone and Sandeep Potluri and Tamas Ordog and Robertson, {Keith D.} and Marks, {David L.} and Fernandez-Zapico, {Martin E.} and Alexandre Gaspar-Maia and Patnaik, {Mrinal M.}",
note = "Funding Information: This work was supported in part by grants from the Gerstner Family Career Development Award (M.B., M.M.P.), the Mayo Clinic Center for Individualized Medicine (M.M.P.), the Henry J. Predolin Foundation for Research in Leukemia (M.M.P.), a Clinical and Translational Science Award (Mentored Career Development Award TR000136) from the National Center for Advancing Translational Science (M.M.P.), the Mayo Clinic Ovarian Cancer SPORE (A.G.M., CA136393), and the DoD Ovarian Cancer Academy (A.G.M.). We thank Dr. Jeong Heon Lee and the staff of the Mayo Clinic Center for Individualized Medicine{\textquoteright}s Epigenomics Development Laboratory for their support. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: This work was supported in part by grants from the Gerstner Family Career Development Award (M.B., M.M.P.), the Mayo Clinic Center for Individualized Medicine (M.M.P.), the Henry J. Predolin Foundation for Research in Leukemia (M.M.P.), a Clinical and Translational Science Award (Mentored Career Development Award TR000136) from the National Center for Advancing Translational Science (M.M.P.), the Mayo Clinic Ovarian Cancer SPORE (A.G.M., CA136393), and the DoD Ovarian Cancer Academy (A.G.M.). We thank Dr. Jeong Heon Lee and the staff of the Mayo Clinic Center for Individualized Medicine?s Epigenomics Development Laboratory for their support. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s41467-022-29142-6",
language = "English (US)",
volume = "13",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}