Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Telebar, F.
Chronic myelomonocytic leukemia with mutations in RAS and inactivation of EZH2: the role of AKT-signaling.
[ Diplomarbeit/Master Thesis (UNI) ] TU Graz; 2022. pp.91.
- Autor*innen der Med Uni Graz:
- Telebar-Zbulj Franciska
- Betreuer*innen:
- Reinisch Andreas
- Zebisch Armin
- Altmetrics:
- Abstract:
- CMML or chronic myelomonocytic leukemia is a clonal hematopoietic stem cell disorder characterized by increased proliferation and myelomonocytic lineage commitment. CMML is characterized by mutations in different gene sets, with the most important for developing CMML in genes encoding epigenetic regulators, splicing factors, and signaling molecules. RAS proteins play a significant role in essential cellular functions such as control of proliferation, differentiation, and apoptosis induction. The most abundant mutations of RAS in CMML are NRAS mutations, followed by KRAS mutations and mutations in the RAS modulators CBL, NF1, and PTPN11. EZH2 is an enzymatic subunit of the Polycomb repressive complex 2 (PRC2). EZH2 catalyzes the trimethylation of histone H3 at lysine 27 (H3K27) and thereby causes the transcriptional repression of its downstream target genes. RASmut EZH2inact frequently co-occurrence together in CMML patients. This leads to the hyperactivation of the ERK pathway and shows higher sensitivity to pharmacological inhibition with MEK inhibitors compared to RASmut CMML. Further, in lung adenocarcinoma with KRAS mutation and EZH2 inactivation, this also leads to the hyperactivation of the AKT pathway.