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Chronic FLT3-ITD signaling in acute myeloid leukemia is connected to a specific chromatin signature
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Cauchy, Pierre, James, Sally R., Zacarias-Cabeza, Joaquin, Ptasinska, Anetta, Imperato, Maria Rosaria, Assi, Salam A., Piper, Jason, Canestraro, Martina, Hoogenkamp, Maarten, Raghavan, Manoj, Loke, Justin, Akiki, Susanna, Clokie, Samuel J. H., Richards, Stephen J., Westhead, David R., Griffiths, Michael J., Ott, Sascha, Bonifer, Constanze and Cockerill, Peter N. (2015) Chronic FLT3-ITD signaling in acute myeloid leukemia is connected to a specific chromatin signature. Cell reports, 12 (5). pp. 821-836. doi:10.1016/j.celrep.2015.06.069 ISSN 2211-1247.
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Official URL: http://dx.doi.org/10.1016/j.celrep.2015.06.069
Abstract
Acute myeloid leukemia (AML) is characterized by recurrent mutations that affect the epigenetic regulatory machinery and signaling molecules, leading to a block in hematopoietic differentiation. Constitutive signaling from mutated growth factor receptors is a major driver of leukemic growth, but how aberrant signaling affects the epigenome in AML is less understood. Furthermore, AML cells undergo extensive clonal evolution, and the mutations in signaling genes are often secondary events. To elucidate how chronic growth factor signaling alters the transcriptional network in AML, we performed a system-wide multi-omics study of primary cells from patients suffering from AML with internal tandem duplications in the FLT3 transmembrane domain (FLT3-ITD). This strategy revealed cooperation between the MAP kinase (MAPK) inducible transcription factor AP-1 and RUNX1 as a major driver of a common, FLT3-ITD-specific gene expression and chromatin signature, demonstrating a major impact of MAPK signaling pathways in shaping the epigenome of FLT3-ITD AML.
Item Type: | Journal Article | ||||||||||||
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Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) | ||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Research Centres > Warwick Systems Biology Centre | ||||||||||||
Library of Congress Subject Headings (LCSH): | Leukemia -- Immunological aspects | ||||||||||||
Journal or Publication Title: | Cell reports | ||||||||||||
Publisher: | Elsevier Inc. | ||||||||||||
ISSN: | 2211-1247 | ||||||||||||
Official Date: | 4 August 2015 | ||||||||||||
Dates: |
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Volume: | 12 | ||||||||||||
Number: | 5 | ||||||||||||
Number of Pages: | 16 | ||||||||||||
Page Range: | pp. 821-836 | ||||||||||||
DOI: | 10.1016/j.celrep.2015.06.069 | ||||||||||||
Status: | Peer Reviewed | ||||||||||||
Publication Status: | Published | ||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||
Date of first compliant deposit: | 30 December 2015 | ||||||||||||
Date of first compliant Open Access: | 30 December 2015 | ||||||||||||
Funder: | Leukaemia & Lymphoma Research (LLR), Kay Kendall Leukemia Fund, Engineering and Physical Sciences Research Council (EPSRC) |
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