Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Zebisch, A; Haller, M; Hiden, K; Goebel, T; Hoefler, G; Troppmair, J; Sill, H.
Loss of RAF kinase inhibitor protein is a somatic event in the pathogenesis of therapy-related acute myeloid leukemias with C-RAF germline mutations.
Leukemia. 2009; 23(6): 1049-1053.
Doi: 10.1038/leu.2009.68
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- Führende Autor*innen der Med Uni Graz
- Sill Heinz
- Zebisch Armin
- Co-Autor*innen der Med Uni Graz
- Höfler Gerald
- Lind Karin
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- Abstract:
- We recently described oncogenic and anti-apoptotic C-RAF germline mutations in patients with therapy-related acute myeloid leukemia (t-AML). Activation of the RAF effector ERK was restricted to transformed cells, suggesting the requirement for cooperating events in leukemogenesis. Western blot analysis of blast cells from patients with C-RAF germline mutations revealed loss of the tumor and metastasis suppressor RAF kinase inhibitor protein (RKIP). Immunohistochemistry of the patients' primary tumors revealed normal RKIP expression levels, indicating that the loss of RKIP is a somatic, t-AML-specific event. In focus formation assays, the oncogenic potential of human mutant C-RAF was strongly influenced by expression levels of RKIP. Although the number of colonies formed by C-RAF(S427G) was significantly increased by RKIP silencing, the opposite was observed after RKIP overexpression. These results show that the loss of RKIP is a functional somatic event in carriers of C-RAF germline mutations, which contributes to the development of t-AML.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Blast Crisis - pathology
- Cell Transformation, Neoplastic -
- Germ-Line Mutation -
- Humans -
- Leukemia, Myeloid, Acute - etiology
- Male -
- Mutation, Missense -
- Neoplasms, Second Primary - etiology
- Phosphatidylethanolamine Binding Protein - deficiency
- Proto-Oncogene Proteins c-raf - genetics
- Find related publications in this database (Keywords)
- therapy-related acute myeloid leukemia
- predisposition
- RKIP
- C-RAF