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AML1-ETO rapidly induces acute myeloblastic leukemia in cooperation with the Wilms tumor gene, WT1.
- Source :
-
Blood [Blood] 2006 Apr 15; Vol. 107 (8), pp. 3303-12. Date of Electronic Publication: 2005 Dec 27. - Publication Year :
- 2006
-
Abstract
- AML1-ETO, a chimeric gene frequently detected in acute myelogenous leukemia (AML), inhibits the differentiation of myeloid progenitors by suppressing genes associated with myeloid differentiation and increases the replating ability of clonogenic myeloid progenitors. However, AML1-ETO alone cannot induce AML and thus additional genetic events are required for the onset of AML. The Wilms tumor gene (WT1), which has been identified as the gene responsible for Wilms tumor, is expressed at high levels in almost all human leukemias. In this study, we have generated transgenic mice (WT1-Tg) that overexpress WT1 in hematopoietic cells to investigate the effects of WT1 on AML1-ETO-associated leukemogenesis. AML1-ETO-transduced bone marrow (BM) cells from WT1-Tg mice exhibited inhibition of myeloid differentiation at more immature stages and higher in vitro colony-forming ability compared with AML1-ETO-transduced BM cells from wild-type mice. Most importantly, all of the mice that received a transplant of AML1-ETO-transduced BM cells from the WT1-Tg mice rapidly developed AML. These results demonstrate that AML1-ETO may exert its leukemogenic function in cooperation with the expression of WT1.
- Subjects :
- Animals
Bone Marrow Transplantation methods
Core Binding Factor Alpha 2 Subunit metabolism
Humans
Leukemia, Myeloid, Acute metabolism
Leukemia, Myeloid, Acute pathology
Mice
Mice, Transgenic
Myeloid Progenitor Cells pathology
Neoplastic Stem Cells metabolism
Neoplastic Stem Cells pathology
Oncogene Proteins, Fusion metabolism
RUNX1 Translocation Partner 1 Protein
Transduction, Genetic
WT1 Proteins metabolism
Cell Differentiation genetics
Cell Transformation, Neoplastic genetics
Core Binding Factor Alpha 2 Subunit genetics
Leukemia, Myeloid, Acute genetics
Myeloid Progenitor Cells metabolism
Oncogene Proteins, Fusion genetics
WT1 Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 107
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 16380455
- Full Text :
- https://doi.org/10.1182/blood-2005-04-1656