Research Paper Volume 12, Issue 24 pp 24734—24777
Biological characteristics of aging in human acute myeloid leukemia cells: the possible importance of aldehyde dehydrogenase, the cytoskeleton and altered transcriptional regulation
- 1 Department of Clinical Science, University of Bergen, Bergen 5021, Norway
- 2 The Proteomics Facility of the University of Bergen (PROBE), University of Bergen, Bergen 5009, Norway
- 3 The Department of Biomedicine, University of Bergen, Bergen 5009, Norway
Received: September 4, 2020 Accepted: November 20, 2020 Published: December 20, 2020https://doi.org/10.18632/aging.202361
How to Cite
Copyright: © 2020 Hernandez-Valladares et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Patients with acute myeloid leukemia (AML) have a median age of 65-70 years at diagnosis. Elderly patients have more chemoresistant disease, and this is partly due to decreased frequencies of favorable and increased frequencies of adverse genetic abnormalities. However, aging-dependent differences may also contribute. We therefore compared AML cell proteomic and phosphoproteomic profiles for (i) elderly low-risk and younger low-risk patients with favorable genetic abnormalities; and (ii) high-risk patients with adverse genetic abnormalities and a higher median age against all low-risk patients with lower median age. Elderly low-risk and younger low-risk patients showed mainly phosphoproteomic differences especially involving transcriptional regulators and cytoskeleton. When comparing high-risk and low-risk patients both proteomic and phosphoproteomic studies showed differences involving cytoskeleton and immunoregulation but also transcriptional regulation and cell division. The age-associated prognostic impact of cyclin-dependent kinases was dependent on the cellular context. The protein level of the adverse prognostic biomarker mitochondrial aldehyde dehydrogenase (ALDH2) showed a similar significant upregulation both in elderly low-risk and elderly high-risk patients. Our results suggest that molecular mechanisms associated with cellular aging influence chemoresistance of AML cells, and especially the cytoskeleton function may then influence cellular hallmarks of aging, e.g. mitosis, polarity, intracellular transport and adhesion.