Molecular Pathology of Mixed-Lineage Leukemia

Abstract

Genomic rearrangements of the locus 11q23 are frequently observed in aggressive acute leukemias with poor prognosis. These chromosomal aberrations fuse the mixed-lineage leukemia (MLL) gene to one of more than 50 partners. The resulting mixed-lineage leukemia fusions often code for chimeric transcriptional activators, which are able to transform normal hematopoietic cells through the deregulation of leukemogenic target genes. This review provides a concise overview about the known functions encoded in MLL and the respective fusion partners. Additionally, the roles of some target genes, as well as co-factors of mixed-lineage leukemia fusion proteins, are described with an emphasis on recent advances potentially uncovering novel therapeutic targets.

Keywords:

• leukemia
• mixed-lineage leukemia
• MLL
• MLL fusions
• transformation

Financial & competing interests disclosure

Generous funding is acknowledged by DFG, Mildred-Scheel Stiftung/Deutsche Krebshilfe, Jose-Carreras Leukemia Fund, Curt-Bohnewald-Fond, and Freifrau v. Fritsch Stiftung. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Acknowledgements

First, our apologies go to all scientists whose work could not be recognized here due to space constraints. We would also like to thank all technicians, students, graduates and post-docs in the laboratory past and present.

Additional information

Funding

Generous funding is acknowledged by DFG, Mildred-Scheel Stiftung/Deutsche Krebshilfe, Jose-Carreras Leukemia Fund, Curt-Bohnewald-Fond, and Freifrau v. Fritsch Stiftung. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.