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Open AccessArticle

Myelomonocytic Skewing In Vitro Discriminates Subgroups of Patients with Myelofibrosis with A Different Phenotype, A Different Mutational Profile and Different Prognosis

1
Medical School, Sigmund Freud University, 1020 Vienna, Austria
2
Department of Internal Medicine V with Hematology, Oncology and Palliative Care, Hospital Hietzing, 1130 Vienna, Austria
3
Division of Hematology and Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, 1090 Vienna, Austria
4
Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria
5
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria
6
Clinical Institute of Pathology, Medical University of Vienna, 1090 Vienna, Austria
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(8), 2291; https://doi.org/10.3390/cancers12082291
Received: 19 June 2020 / Revised: 6 August 2020 / Accepted: 13 August 2020 / Published: 14 August 2020
(This article belongs to the Special Issue New Insights into Myeloproliferative Neoplasms)
Normal hematopoietic function is maintained by a well-controlled balance of myelomonocytic, megaerythroid and lymphoid progenitor cell populations which may be skewed during pathologic conditions. Using semisolid in vitro cultures supporting the growth of myelomonocytic (CFU-GM) and erythroid (BFU-E) colonies, we investigated skewed differentiation towards the myelomonocytic over erythroid commitment in 81 patients with myelofibrosis (MF). MF patients had significantly increased numbers of circulating CFU-GM and BFU-E. Myelomonocytic skewing as indicated by a CFU-GM/BFU-E ratio ≥ 1 was found in 26/81 (32%) MF patients as compared to 1/98 (1%) in normal individuals. Patients with myelomonocytic skewing as compared to patients without skewing had higher white blood cell and blast cell counts, more frequent leukoerythroblastic features, but lower hemoglobin levels and platelet counts. The presence of myelomonocytic skewing was associated with a higher frequency of additional mutations, particularly in genes of the epigenetic and/or splicing machinery, and a significantly shorter survival (46 vs. 138 mo, p < 0.001). The results of this study show that the in vitro detection of myelomonocytic skewing can discriminate subgroups of patients with MF with a different phenotype, a different mutational profile and a different prognosis. Our findings may be important for the understanding and management of MF. View Full-Text
Keywords: myelofibrosis; skewing; progenitor cells; in vitro culture; hematopoiesis; prognosis myelofibrosis; skewing; progenitor cells; in vitro culture; hematopoiesis; prognosis
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Geissler, K.; Gisslinger, B.; Jäger, E.; Jäger, R.; Schiefer, A.-I.; Bogner, E.; Fuchs, E.; Schischlik, F.; Alpar, D.; Simonitsch-Klupp, I.; Kralovics, R.; Gisslinger, H. Myelomonocytic Skewing In Vitro Discriminates Subgroups of Patients with Myelofibrosis with A Different Phenotype, A Different Mutational Profile and Different Prognosis. Cancers 2020, 12, 2291.

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