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PFKFB4 is critical for the survival of acute monocytic leukemia cells
- Source :
- Biochemical and Biophysical Research Communications. 526:978-985
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Acute myeloid leukemia (AML), which is characterized by an overproliferation of blood cells, is divided into several subtypes in adults and children. Of those subtypes, acute monocytic leukemia (M4/M5, AMoL) is reported to be associated with abnormal gene fusions that result in monocytic cell differentiation being blocked. However, few studies have shown a relationship between cellular metabolism and the initiation of AMoL. Here, we use the open-access database TCGA to analyze the expression of enzymes in the metabolic cycle and find that PFKFB4 is highly expressed in AMoL. Subsequently, knocking down PFKFB4 in THP-1 and U937 cells significantly inhibits cell growth and increases the sensitivity of cells to chemical drug-induced apoptosis. In line with the gene-editing alterations, treatment with a PFKFB4 inhibitor exhibits similar effects on THP-1 and U937 proliferation and apoptosis. In addition, we find that PFKFB4 functions as a reliable target of the epigenetic regulator MLL, which is a well-known modulator in AMoL. Mechanistically, MLL promotes PFKFB4 expression at the transcriptional level through the putative E2F6 binding site in the promoter of the pfkfb4 gene. Taken together, our results suggest PFKFB4 serves as a downstream target of MLL and functions as a potent therapeutic target in AMoL.
- Subjects :
- 0301 basic medicine
Transcription, Genetic
Cell Survival
Phosphofructokinase-2
THP-1 Cells
Cellular differentiation
Biophysics
Apoptosis
Biology
Biochemistry
03 medical and health sciences
0302 clinical medicine
medicine
Humans
Gene Silencing
Acute monocytic leukemia
Epigenetics
Protein Kinase Inhibitors
Molecular Biology
Gene
Base Sequence
Gene Expression Regulation, Leukemic
Cell growth
Myeloid leukemia
Histone-Lysine N-Methyltransferase
U937 Cells
Cell Biology
PFKFB4
Prognosis
medicine.disease
030104 developmental biology
030220 oncology & carcinogenesis
Leukemia, Monocytic, Acute
Cancer research
Myeloid-Lymphoid Leukemia Protein
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 526
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....e00eadfa9cdee38ea25145837ea535d1