Alpha-Enolase (ENO1) Promotes AML Progression Via the MAPK/ERK Pathway

Abstract：

Acute Myeloid Leukemia (AML) is a malignant clonal disease of the blood system, characterized by abnormal proliferation and impaired differentiation of myeloid cells, resulting in the accumulation of leukemia cells and abnormal hematopoietic function. Although targeted therapy has developed rapidly, drug resistance and relapse remain major challenges in AML treatment. Exploring the abnormal proteins driving leukemia development and searching for new therapeutic targets and drugs are key tasks for AML treatment.

Enolase-1 (ENO1) is a key enzyme in the glycolysis process, and its abnormal expression drives the development of various cancers. To clarify the role of ENO1 in the progression of AML, we studied the relationship between ENO1 and AML using database and patient transcriptome sequencing datafrom 185 AML patient samples. Our results confirm that ENO1 is highly expressed in AML patients and is associated with poor clinical outcomes. Knockdown of ENO1 in AML cells significantly inhibited their proliferation, cloning, migration, and invasion in vitro, blocked the cell cycle, and promoted apoptosis. We found that ENO1 was closely related to mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway through cell transcriptome sequencing data analysis. ERK pathway inhibitors significantly inhibited proliferation, clonal formation, migration, and invasion of AML cells in vitro, blocked cell cycle, and promoted apoptosis. And knockdown of ENO1 significantly inhibited ERK pathway proteins' phosphorylation. Most importantly, activators of ERK pathway could reverse the effects of ENO1 knockdown on AML cells. We also found that ENO1 knockdown inhibited the proliferation and invasion of AML cells in mice and significantly increase the overall survival rate of mice.

Altogether, these results not only reveal the role and mechanism of ENO1 in the development of AML but also highlight ENO1 as a potential therapeutic target in the treatment of AML.

Key words: AML, ENO1, Cell proliferation, Invasion

No relevant conflicts of interest to declare.