Menin as a hub controlling mixed lineage leukemia

Area of Science:

• Hematology
• Molecular Biology
• Cancer Research

Background:

• Mixed lineage leukemia (MLL) fusion protein (FP)-induced acute leukemia is aggressive and treatment-resistant.
• Menin, a nuclear protein, is implicated in leukemogenesis by interacting with MLL and other proteins.

Purpose of the Study:

• To elucidate the role of menin as a scaffold protein in MLL-FP-induced leukemia.
• To identify novel therapeutic targets within the menin/MLL interaction network and cooperating signaling pathways.

Main Methods:

• Co-crystal structure analysis of the menin-MLL interaction.
• Investigation of menin's role in recruiting MLL and MLL-FPs to target genes.
• Exploration of cooperating signaling pathways like Wnt, GSK3, and Brd4.

Main Results:

• Menin acts as a central scaffold protein, forming a crucial hub with MLL and MLL-FPs.
• Menin facilitates the recruitment of both wild-type MLL and MLL-FPs to target genes.
• The menin/MLL/MLL-FP hub collaborates with Wnt, GSK3, and Brd4 pathways in leukemogenesis.

Conclusions:

• Menin is a critical component of the MLL-FP leukemogenic machinery.
• Targeting the menin/MLL hub and its associated pathways presents a promising therapeutic avenue for MLL-FP leukemias.