MBP1 inhibits AML proliferation through downregulating noncanonical Wnt/Ca²⁺ signaling pathway

Area of Science:

• Oncology
• Molecular Biology
• Cancer Genetics

Background:

• Acute myeloid leukemia (AML) presents significant therapeutic challenges, necessitating novel treatment strategies.
• The role of the ENO1 short variant, MBP1, in AML pathogenesis was previously uncharacterized.

Purpose of the Study:

• To investigate the functional role of MBP1 in AML.
• To elucidate the molecular mechanisms underlying MBP1's effect on AML.
• To evaluate MBP1 as a potential therapeutic target in AML.

Main Methods:

• Analysis of MBP1 and ENO1 expression in primary AML patient samples.
• In vitro functional assays (proliferation, apoptosis, cell cycle) in AML cell lines with restored MBP1.
• RNA-sequencing and pathway analysis to identify MBP1-regulated pathways.
• In vivo mouse xenograft models to assess MBP1's effect on AML progression.

Main Results:

• MBP1 was significantly downregulated, while ENO1 was upregulated in AML patients, indicating an imbalanced ENO1/MBP1 ratio.
• Restoring MBP1 expression in AML cell lines inhibited proliferation, colony formation, induced apoptosis, and caused G1 cell cycle arrest.
• MBP1 overexpression suppressed the non-canonical Wnt/Ca²⁺ signaling pathway by downregulating Wnt11 and NFATc1.
• In vivo studies confirmed that MBP1 overexpression attenuated AML progression and reduced tumor burden.

Conclusions:

• MBP1 deficiency promotes AML development and progression, likely through activation of the Wnt11/NFATc1 signaling pathway.
• Restoration of MBP1 exhibits anti-leukemic effects, highlighting its potential as a novel therapeutic target for AML.