Induced myelomonocytic differentiation in leukemia cells is accompanied by noncanonical transcription factor expression

Autor: Andrew Yen, Jeffrey D. Varner, Harmony B. Yourish, Holly A. Jensen, Rodica P. Bunaciu
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Acute promyelocytic leukemia
HL60
QH301-705.5
General Biochemistry
Genetics and Molecular Biology
chemistry.chemical_compound
D3
1
25-dihydroxyvitamin D3
Immunophenotyping
hemic and lymphatic diseases
Research article
medicine
RA
retinoic acid
Gfi-1
growth factor independent protein 1
Oct4
octamer-binding transcription factor 4
Retinoic acid
Lineage selection
Biology (General)
EGR1
early growth response protein 1
Transcription factor
AML
acute myeloid leukemia
IRF-1
interferon regulatory factor 1
biology
U937 cell
PU.1
binds PU-box
also called Spi-1
C/EBPα
CCAAT-enhancer binding protein α
Myeloid leukemia
CD
cluster of differentiation [marker]
medicine.disease
Aryl hydrocarbon receptor
Molecular biology
chemistry
APL
acute promyelocytic leukemia
RARα
retinoic acid receptor α
AhR
aryl hydrocarbon receptor
Differentiation
Immunology
biology.protein
VDR
vitamin D receptor
FAB
French–American–British [myeloid leukemia classification]
Vitamin D3
K562 cells
Zdroj: FEBS Open Bio, Vol 5, Iss 1, Pp 789-800 (2015)
FEBS Open Bio
ISSN: 2211-5463
Popis: Highlights • We surveyed common myeloid leukemia cell lines undergoing differentiation therapy. • Lineage progression in induced leukemia cell lines differs from nonmalignant cells. • Aberrant transcription factor expression occurs in acute myeloid leukemia cells. • A given differentiation therapy elicits different effects in specific cell lines. • Although potent tools, cell lines must be employed with circumspection.
Transcription factors that drive non-neoplastic myelomonocytic differentiation are well characterized but have not been systematically analyzed in the leukemic context. We investigated widely used, patient-derived myeloid leukemia cell lines with proclivity for differentiation into granulocytes by retinoic acid (RA) and/or monocytes by 1,25-dihyrdroxyvitamin D3 (D3). Using K562 (FAB M1), HL60 (FAB M2), RA-resistant HL60 sublines, NB4 (FAB M3), and U937 (FAB M5), we correlated nuclear transcription factor expression to immunophenotype, G1/G0 cell cycle arrest and functional inducible oxidative metabolism. We found that myelomonocytic transcription factors are aberrantly expressed in these cell lines. Monocytic-lineage factor EGR1 was not induced by D3 (the monocytic inducer) but instead by RA (the granulocytic inducer) in lineage bipotent myeloblastic HL60. In promyelocytic NB4 cells, EGR1 levels were increased by D3, while Gfi-1 expression (which promotes the granulocytic lineage) was upregulated during D3-induced monocytic differentiation in HL60, and by RA treatment in monocytic U937 cells. Furthermore, RARα and VDR expression were not strongly correlated to differentiation. In response to different differentiation inducers, U937 exhibited the most distinct transcription factor expression profile, while similarly mature NB4 and HL60 were better coupled. Overall, the differentiation induction agents RA and D3 elicited cell-specific responses across these common FAB M1-M5 cell lines.
Databáze: OpenAIRE
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