Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Zebisch, A; Wölfler, A; Fried, I; Wolf, O; Lind, K; Bodner, C; Haller, M; Drasche, A; Pirkebner, D; Matallanas, D; Rath, O; Blyth, K; Delwel, R; Taskesen, E; Quehenberger, F; Kolch, W; Troppmair, J; Sill, H.
Frequent loss of RAF kinase inhibitor protein expression in acute myeloid leukemia.
Leukemia. 2012; 26(8):1842-1849
Doi: 10.1038/leu.2012.61
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- Führende Autor*innen der Med Uni Graz
- Sill Heinz
- Zebisch Armin
- Co-Autor*innen der Med Uni Graz
- Bodner Claudia
- Fried Isabella
- Lind Karin
- Quehenberger Franz
- Wölfler Albert
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- Abstract:
- RAF kinase inhibitor protein (RKIP) is a negative regulator of the RAS-mitogen-activated protein kinase/extracellular signal-regulated kinase signaling cascade. We investigated its role in acute myeloid leukemia (AML), an aggressive malignancy arising from hematopoietic stem and progenitor cells (HSPCs). Western blot analysis revealed loss of RKIP expression in 19/103 (18%) primary AML samples and 4/17 (24%) AML cell lines but not in 10 CD34+ HSPC specimens. In in-vitro experiments with myeloid cell lines, RKIP overexpression inhibited cellular proliferation and colony formation in soft agar. Analysis of two cohorts with 103 and 285 AML patients, respectively, established a correlation of decreased RKIP expression with monocytic phenotypes. RKIP loss was associated with RAS mutations and in transformation assays, RKIP decreased the oncogenic potential of mutant RAS. Loss of RKIP further related to a significantly longer relapse-free survival and overall survival in uni- and multivariate analyses. Our data show that RKIP is frequently lost in AML and correlates with monocytic phenotypes and mutations in RAS. RKIP inhibits proliferation and transformation of myeloid cells and decreases transformation induced by mutant RAS. Finally, loss of RKIP seems to be a favorable prognostic parameter in patients with AML.
- Find related publications in this database (using NLM MeSH Indexing)
- Cell Differentiation - genetics
- Cell Line, Tumor -
- Cell Proliferation -
- Cell Transformation, Neoplastic - genetics
- Gene Expression Regulation, Leukemic -
- Genes, ras -
- Humans -
- Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - metabolism Leukemia, Myeloid, Acute - mortality
- Monocytes - cytology Monocytes - metabolism
- Mutation -
- Myeloid Cells - metabolism
- Phosphatidylethanolamine Binding Protein - deficiency Phosphatidylethanolamine Binding Protein - genetics Phosphatidylethanolamine Binding Protein - metabolism
- Prognosis -
- Find related publications in this database (Keywords)
- RAF kinase inhibitor protein
- acute myeloid leukemia
- RAS mutation