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Heterogeneous sensitivity of human acute myeloid leukemia to β-catenin down-modulation.
- Source :
- Leukemia (08876924); May2011, Vol. 25 Issue 5, p770-780, 11p, 4 Charts, 5 Graphs
- Publication Year :
- 2011
-
Abstract
- Dysregulation of the Wnt/β-catenin pathway has been observed in various malignancies, including acute myeloid leukemia (AML), where the overexpression of β-catenin is an independent adverse prognostic factor. β-catenin was found upregulated in the vast majority of AML samples and more frequently localized in the nucleus of leukemic stem cells compared with normal bone marrow CD34(+) cells. The knockdown of β-catenin, using a short hairpin RNA (shRNA) lentiviral approach, accelerates all-trans retinoic acid-induced differentiation and impairs the proliferation of HL60 leukemic cell line. Using in vivo quantitative tracking of these cells, we observed a reduced engraftment potential after xenotransplantation when β-catenin was silenced. However, when studying primary AML cells, despite effective downregulation of β-catenin we did not observe any impairment of their in vitro long-term maintenance on MS-5 stroma nor of their engraftment potential in vivo. Altogether, these results show that despite a frequent β-catenin upregulation in AML, leukemia-initiating cells might not be 'addicted' to this pathway and thus targeted therapy against β-catenin might not be successful in all patients. [ABSTRACT FROM AUTHOR]
- Subjects :
- ACUTE myeloid leukemia
MYELOID leukemia
XENOTRANSPLANTATION
LEUKEMIA
NERVE tissue proteins
ANIMAL experimentation
APOPTOSIS
BIOCHEMISTRY
CELL cycle
CELL differentiation
CELL physiology
CELLULAR signal transduction
COMPARATIVE studies
CYTOSKELETAL proteins
FLOW cytometry
PHENOMENOLOGY
RESEARCH methodology
MEDICAL cooperation
MICE
POLYMERASE chain reaction
RESEARCH
RESEARCH funding
RNA
WESTERN immunoblotting
XENOGRAFTS
EVALUATION research
REVERSE transcriptase polymerase chain reaction
CANCER cell culture
Subjects
Details
- Language :
- English
- ISSN :
- 08876924
- Volume :
- 25
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Leukemia (08876924)
- Publication Type :
- Academic Journal
- Accession number :
- 60513809
- Full Text :
- https://doi.org/10.1038/leu.2011.17