MLL: how complex does it get?

Area of Science:

• Molecular Biology
• Genetics
• Hematology

Background:

• The mixed lineage leukemia (MLL) gene encodes a large nuclear protein, a homolog of Drosophila trithorax.
• MLL is essential for maintaining HOX gene expression during development and hematopoiesis.
• MLL's precise regulatory role in HOX gene expression, likely involving chromatin organization, is not fully understood.

Purpose of the Study:

• To review the progress in understanding the function of the wild-type MLL protein.
• To explore the insights gained from MLL-containing protein complexes and gain/loss-of-function experiments.
• To address the remaining questions regarding MLL's multifaceted functions.

Main Methods:

• Literature review of studies on MLL gene function.
• Analysis of findings from isolated MLL-containing protein complexes.
• Examination of data from gain- and loss-of-function experiments.

Main Results:

• MLL is vital for HOX gene expression and hematopoietic development.
• MLL gene rearrangements are common in acute leukemias, affecting both lymphoid and myeloid lineages.
• Mutations in MLL are associated with infant and secondary leukemias, suggesting a role in early development.

Conclusions:

• Significant advances have been made in understanding MLL protein function.
• MLL plays a critical role in early hematopoietic development and HOX gene regulation.
• Despite progress, many challenging questions about MLL's function and its role in leukemia persist.