کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2827962 | 1162473 | 2007 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inability of RUNX1/AML1 to breach AML1-ETO block of embryonic stem cell definitive hematopoiesis
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Inability of RUNX1/AML1 to breach AML1-ETO block of embryonic stem cell definitive hematopoiesis Inability of RUNX1/AML1 to breach AML1-ETO block of embryonic stem cell definitive hematopoiesis](/preview/png/2827962.png)
چکیده انگلیسی
The t(8;21)(q22:q22) translocation associated with acute myeloid leukemia fuses the AML1/RUNX1 N-terminal portion located on chromosome 21 to most of the ETO/MTG8 gene on chromosome 8. Various investigators have shown that the fusion product AML1-ETO on its own is unable to promote leukemia. Early studies using transgenic mouse models demonstrated that the direct knock-in of the fusion protein expression is embryonic lethal, similar to the AML1 knockout, suggesting that AML1-ETO has a dominant negative role over AML1. Using the embryonic stem cells generated for such studies, we show here that the presence of the fusion product AML1-ETO blocks definitive hematopoiesis in vitro as well, in both one and two step methylcellulose methods of embryonic stem cell hematopoietic differentiation. However, there is a very low occurrence of macrophage colonies, similar to the knock-in mice that display macrophages in cell cultures of yolk sac derived cells. In addition, we show that exogenous expression of AML1 is unable to bypass this AML1-ETO induced definitive hematopoietic block in these cells. This inability is not linked to an inability to reverse gene expression inhibition by AML1-ETO of the PU.1 gene associated with stem cell maintenance and myeloid differentiation. Our results suggest that AML1-ETO functions in a complex competitive manner with AML1 involving transcriptional regulation, protein-protein interactions and post-transcriptional mechanism(s) affecting early embryonic hematopoiesis and possibly leukemogenesis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Blood Cells, Molecules, and Diseases - Volume 39, Issue 3, NovemberâDecember 2007, Pages 321-328
Journal: Blood Cells, Molecules, and Diseases - Volume 39, Issue 3, NovemberâDecember 2007, Pages 321-328
نویسندگان
Luke F. Peterson, Miao-Chia Lo, Akiko Joo Okumura, Dong-Er Zhang,