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Licensed to elongate: a molecular mechanism for MLL-based leukaemogenesis

Nature Reviews Cancer volume 10, pages 721–728 (2010)Cite this article

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Abstract

The RNA polymerase II (Pol II) elongation factor (ELL) was the first translocation partner of mixed lineage leukaemia (MLL) for which a biochemical function was determined. It was therefore proposed that the regulation of the elongation stage of transcription could be fundamental to MLL-based leukaemogenesis. Recent studies have identified ELL complexed with several of the translocation partners of MLL in a transcriptional super elongation complex (SEC). These studies provide evidence for the importance of the regulation of Pol II elongation in disease pathogenesis and suggest that MLL chimaeras function by licensing Pol II transcription elongation without the appropriate checkpoints.

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Figure 1: The subunit composition for the histone H3K4 methylases COMPASS and COMPASS-like complexes from yeast to human.
Figure 2: The most common MLL chimaeras found in acute leukaemia.
Figure 3: Licensed to elongate, a molecular mechanism for MLL-based leukaemogenesis.

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Acknowledgements

The authors would like to thank E. Smith, A. Gamis and E. Park for conversations, suggestions and critical reading of the manuscript. They also thank L. Shilatifard for editorial assistance. C.L. is a graduate student registered with the Open University. The studies in the Shilatifard laboratory are supported in part by grants from Alex's Lemonade Stand Foundation to E.G. and from the US National Institute of Health grants R01GM069905, R01CA150265 and R01CA89455 to A.S.

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  1. Man Mohan, Chengqi Lin, Erin Guest and Ali Shilatifard are at the Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA.,

    Man Mohan, Chengqi Lin, Erin Guest & Ali Shilatifard

  2. Erin Guest is also at the Children's Mercy Hospital, 2401 Gillham Road, Kansas City, Missouri 64108, USA.,

    Erin Guest

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Glossary

Multidimensional protein identification technology

(MudPIT). This is a sensitive mass spectrometric method used for the identification of complex mixtures of proteins.

YEATS domain

The YEATS domain proteins are a diverse family of proteins conserved from yeast to human, which function in chromatin modifications and remodelling, and transcriptional regulation. The name for this family of proteins is derived from the first five proteins (YAF9, ENL, AF9, TAF14 and SAS5) that were discovered to have this domain.

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Mohan, M., Lin, C., Guest, E. et al. Licensed to elongate: a molecular mechanism for MLL-based leukaemogenesis. Nat Rev Cancer 10, 721–728 (2010). https://doi.org/10.1038/nrc2915

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