PFKFB3 as a potential therapeutic target in acute myeloid leukaemia

Zhuoma, Suonan 2022. PFKFB3 as a potential therapeutic target in acute myeloid leukaemia. MPhil Thesis, Cardiff University. Item availability restricted.

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Abstract

NADPH oxidase 2 (NOX2) derived reactive oxygen species (ROS) play an important role in cancer cell signalling, proliferation, differentiation, and survival. Higher levels of extracellular derived ROS are known to be present in acute myeloid leukaemia (AML) patients’ blasts compared to normal haematopoietic cells. In a human haematopoietic progenitor cell model, elevated ROS led to increased extracellular lactate production and glucose uptake, and proteins that critically regulate glycolytic enzymes 6- phosphofructo-2-kinase/fructose-2,6-bisphosphate enzyme 3 (PFKFB3). However, little is known regarding the expression levels or role of PFKFB family members in normal haematopoiesis and AML. My analysis from online transcriptome data (Bloodspot and TCGA databases) revealed that PFKFB3 and PFKFB4 mRNA significantly increased with differentiation. PFKFB3 mRNA expression is significantly higher in AML with complexes cytogenetics than in all PFKFBs in haematopoietic stem cell (HSC). PFKFB3 mRNA expression level does not corelate with overall survival. PFKFB3 mRNA expression level corelates with Cytochrome b-245 beta chain (CYBB) expression in AML patients. I found that NOMO-1 cells produced the highest ROS and PFKFB3 in AML cell lines. By using Western blotting and Diogenes, I found a positive correlation between ROS and expressed PFKFB3 in AML cell lines. However, singlecell PFKFB3 flow cytometry detection failed because antibody may bind nuclear PFKFB3 with less efficiency than cytosolic in some cell lines. In summary, this study supports the evidence that ROS-increased glycolysis and metabolic reprogramming are associated with PFKFB3 in AML, but more experimental validation is needed.

Item Type:	Thesis (MPhil)
Date Type:	Completion
Status:	Unpublished
Schools:	Medicine
Date of First Compliant Deposit:	18 April 2023
Last Modified:	06 Jan 2024 02:20
URI:	https://orca.cardiff.ac.uk/id/eprint/158914

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