کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10907277 | 1087399 | 2016 | 28 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Epigenetic therapy as a novel approach for GFI136N-associated murine/human AML
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
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چکیده انگلیسی
Epigenetic changes can contribute to development of acute myeloid leukemia (AML), a malignant disease of the bone marrow. A single-nucleotide polymorphism of transcription factor growth factor independence 1 (GFI1) generates a protein with an asparagine at position 36 (GFI136N) instead of a serine at position 36 (GFI136S), which is associated with de novo AML in humans. However, how GFI136N predisposes to AML is poorly understood. To explore the mechanism, we used knock-in mouse strains expressing GFI136N or GFI136S. Presence of GFI136N shortened the latency and increased the incidence of AML in different murine models of myelodysplastic syndrome/AML. On a molecular level, GFI136N induced genomewide epigenetic changes, leading to expression of AML-associated genes. On a therapeutic level, use of histone acetyltransferase inhibitors specifically impeded growth of GFI136N-expressing human and murine AML cells in vitro and in vivo. These results establish, as a proof of principle, how epigenetic changes in GFI136N-induced AML can be targeted.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Hematology - Volume 44, Issue 8, August 2016, Pages 713-726.e14
Journal: Experimental Hematology - Volume 44, Issue 8, August 2016, Pages 713-726.e14
نویسندگان
Lacramioara Botezatu, Lars C. Michel, Anne Helness, Charles Vadnais, Hideki Makishima, Judith M. Hönes, François Robert, Lothar Vassen, Aniththa Thivakaran, Yahya Al-Matary, Robert F. Lams, Judith Schütte, Bernd Giebel, André Görgens,