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The Capacity of Long-Term In Vitro Proliferation of Acute Myeloid Leukemia Cells Supported Only by Exogenous Cytokines Is Associated with a Patient Subset with Adverse Outcome

1
Department of Medicine, Haukeland University Hospital; 5021 Bergen, Norway
2
Section for Hematology, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway
3
The Proteomics Unit at the University of Bergen, Department of Biomedicine, University of Bergen, 5020 Bergen, Norway
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(1), 73; https://doi.org/10.3390/cancers11010073
Received: 22 November 2018 / Revised: 28 December 2018 / Accepted: 2 January 2019 / Published: 10 January 2019
Acute myeloid leukemia (AML) is an aggressive malignancy, which is highly heterogeneous with regard to chemosensitivity and biological features. The AML cell population is organized in a hierarchy that is reflected in the in vitro growth characteristics, with only a minority of cells being able to proliferate for more than two weeks. In this study, we investigated the ability of AML stem cells to survive and proliferate in suspension cultures in the presence of exogenous mediators but without supporting non-leukemic cells. We saw that a high number of maintained stem cells (i.e., a large number of clonogenic cells after five weeks of culture) was associated with decreased overall survival for patients receiving intensive chemotherapy; this prognostic impact was also detected in the multivariate/adjusted analysis. Furthermore, the patients with many clonogenic cells presented more frequently with mutations in transcription-related genes, and also showed a higher abundance of proteins involved in transcription at the time of diagnosis. In conclusion, the growth characteristics of the long-term proliferating leukemic stem cells seem to have an independent prognostic impact in human AML, and these characteristics appear to be reflected by the mutational landscape and the proteome of the patients at the time of diagnosis. View Full-Text
Keywords: acute myeloid leukemia; clonogenic cells; colony formation; cytokines; differentiation; transcription acute myeloid leukemia; clonogenic cells; colony formation; cytokines; differentiation; transcription
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Brenner, A.K.; Aasebø, E.; Hernandez-Valladares, M.; Selheim, F.; Berven, F.; Grønningsæter, I.-S.; Bartaula-Brevik, S.; Bruserud, Ø. The Capacity of Long-Term In Vitro Proliferation of Acute Myeloid Leukemia Cells Supported Only by Exogenous Cytokines Is Associated with a Patient Subset with Adverse Outcome. Cancers 2019, 11, 73.

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