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Updated: Dec 23, 2025
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
Published on: June 6, 2025
PFKFB4 is critical for the survival of acute monocytic leukemia cells
Gongai Wang1, Shumei Li1, Kewei Xue2
1Department of Hematology, Jining No.1 People's Hospital, No.6, Jiankang Road, Jining City, Shandong Province, 272011, PR China.
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.
Insights
PFKFB4 is highly expressed in acute monocytic leukemia (AMoL), a subtype of acute myeloid leukemia (AML). Inhibiting PFKFB4 or targeting it with drugs significantly reduces cancer cell growth and increases apoptosis, indicating its therapeutic potential.
Area of Science:
- * Hematology
- * Molecular Biology
- * Cancer Metabolism
Background:
- * Acute myeloid leukemia (AML) encompasses various subtypes, including acute monocytic leukemia (AMoL/M4/M5).
- * AMoL is linked to gene fusions blocking monocytic cell differentiation.
- * The role of cellular metabolism in AMoL initiation is underexplored.
Purpose of the Study:
- * To investigate the link between cellular metabolism and AMoL pathogenesis.
- * To identify potential therapeutic targets for AMoL based on metabolic enzyme expression.
Main Methods:
- * Analysis of metabolic enzyme expression in AMoL using The Cancer Genome Atlas (TCGA) database.
- * Gene knockdown experiments targeting PFKFB4 in AMoL cell lines (THP-1, U937).
- * Assessment of cell proliferation and apoptosis following PFKFB4 inhibition (gene editing or drug treatment).
- * Investigation of the regulatory relationship between MLL and PFKFB4.
Main Results:
- * PFKFB4 was found to be highly expressed in AMoL.
- * Knockdown of PFKFB4 significantly inhibited proliferation and enhanced apoptosis in AMoL cell lines.
- * PFKFB4 inhibition using a specific drug mimicked the effects of gene knockdown.
- * PFKFB4 was identified as a downstream target of the epigenetic regulator MLL.
- * MLL was shown to increase PFKFB4 transcription via an E2F6 binding site.
Conclusions:
- * PFKFB4 plays a crucial role in AMoL cell growth and survival.
- * PFKFB4 is a downstream target regulated by MLL in AMoL.
- * PFKFB4 represents a promising therapeutic target for treating AMoL.
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