Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Geissler, K; Jäger, E; Barna, A; Gurbisz, M; Marschon, R; Graf, T; Nösslinger, T; Pfeilstöcker, M; Machherndl-Spandl, S; Stauder, R; Zebisch, A; Sill, H; Öhler, L; Kusec, R; Hoermann, G; Valent, P.
Multistep pathogenesis of chronic myelomonocytic leukemia in patients.
Eur J Haematol. 2022; 109(1):50-57
Doi: 10.1111/ejh.13768
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- Co-Autor*innen der Med Uni Graz
- Sill Heinz
- Zebisch Armin
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- Abstract:
- BACKGROUND: A multistep pathogenesis of myeloid leukemia including mutations in epigenetic, spliceosome, and signaling genes has been recently demonstrated in a preclinical model but is poorly validated in patients. METHODS: Clinical, phenotypic, and biologic features were compared between three distinct molecularly defined CMML cohorts including TET2 monomutated patients (T, n = 10), TET2/SRSF2 bimutated patients (TS, n = 19), and patients who had NRAS mutations in addition to TET2/SRSF2 comutations (TSN, n = 14). RESULTS: Median survival was 90, 45, and 9 months, respectively (p = .001). Whereas no patient in the T and TS group transformed into acute myeloid leukemia (AML), 6/14 patients in the TSN group had AML at study entry or transformed during follow-up. Leukocyte counts, blast cell counts, and LDH levels were significantly higher in TSN vs. TS and T, respectively, whereas hemoglobin and platelet values were not significantly different. Increased growth factor-independent myeloid colony formation was restricted to TSN but not found in T and TS, respectively. The proportion of patients showing in vitro myelomonocytic skewing in T, TS, and TSN was 0%, 56%, and 100%, respectively (p = .010). CONCLUSION: Our results demonstrate that the model of multistep pathogenesis in CMML can be recapitulated in patients regarding clinical, phenotypic, and biologic features.
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- Biological Products - administration & dosage
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- CMML
- NRAS
- pathogenesis
- SRSF2
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