Biological characteristics of aging in human acute myeloid leukemia cells: the possible importance of aldehyde dehydrogenase, the cytoskeleton and altered transcriptional regulation.
Adult
Age Factors
Aged
Aged, 80 and over
Aging
/ genetics
Aldehyde Dehydrogenase, Mitochondrial
/ genetics
Cell Adhesion
/ genetics
Cell Polarity
Cellular Senescence
/ genetics
Cytoskeleton
/ metabolism
Drug Resistance, Neoplasm
/ genetics
Female
Gene Expression Regulation, Leukemic
Humans
Leukemia, Myeloid, Acute
/ drug therapy
Male
Middle Aged
Mitosis
/ genetics
Phosphoproteins
Prognosis
Proteomics
Risk Factors
Up-Regulation
ALDH2
acute myeloid leukenia
age
cytogenetics
risk
Journal
Aging
ISSN: 1945-4589
Titre abrégé: Aging (Albany NY)
Pays: United States
ID NLM: 101508617
Informations de publication
Date de publication:
20 12 2020
20 12 2020
Historique:
received:
04
09
2020
accepted:
20
11
2020
pubmed:
23
12
2020
medline:
26
5
2021
entrez:
22
12
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33349623
pii: 202361
doi: 10.18632/aging.202361
pmc: PMC7803495
doi:
Substances chimiques
Phosphoproteins
0
ALDH2 protein, human
EC 1.2.1.3
Aldehyde Dehydrogenase, Mitochondrial
EC 1.2.1.3
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
24734-24777Références
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