Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Rearrangements of the mixed lineage leukemia gene MLL are associated with aggressive lymphoid and myeloid leukemias. The resulting MLL fusion proteins enforce high-level expression of HOX genes and the HOX cofactor MEIS1, which is pivotal for leukemogenesis. Both wild-type MLL and MLL fusion proteins interact with the tumor suppressor menin and with the Hoxa9 locus in vivo. Here, we show that MLL sequences between amino acids 5 and 44 are required for interaction with menin and for the transformation of hematopoietic progenitors. Blocking the MLL-menin interaction by the expression of a dominant negative inhibitor composed of amino terminal MLL sequences down-regulates Meis1 expression and inhibits cell proliferation, suggesting that targeting this interaction may be an effective therapeutic strategy for leukemias with MLL rearrangements.

Original publication

DOI

10.1158/0008-5472.CAN-06-2369

Type

Journal article

Journal

Cancer Res

Publication Date

01/08/2007

Volume

67

Pages

7275 - 7283

Keywords

Cell Proliferation, Cell Transformation, Neoplastic, Cells, Cultured, Chromatin Immunoprecipitation, Down-Regulation, Gene Expression, Histone-Lysine N-Methyltransferase, Homeodomain Proteins, Humans, Immunoprecipitation, Kidney, Leukemia, Myeloid, Myeloid-Lymphoid Leukemia Protein, Neoplasm Proteins, Polymerase Chain Reaction, Proto-Oncogene Proteins