The role of menin in hematopoiesis.
In the hematopoietic system, menin was found to interact with MLL, a large protein encoded by the mixed linage leukemia gene that acts as a histone H3 methyltransferase. The MLL gene is a recurrent target for translocations in both acute myeloid and acute lymphoid leukemias. MLL gene rearrangements involve a variety of translocation partners, giving rise to MLL fusion proteins whose transforming ability is mediated through upregulated expression of Homeobox (Hox) genes as well as other targets. Recent work indicates that menin is an essential partner of MLL fusion proteins in leukemic cells and that it regulates normal hematopoiesis. In the absence of menin, steady-state hematopoiesis is largely preserved; however, menin-deficient hematopoietic stem cells are markedly deficient in situations of hematopoietic stress, such as during recovery after bone marrow transplantation. In leukemias driven by MLL fusion proteins, menin is essential for transformation and growth of the malignant cells. Thus, menin-MLL interactions represent a promising therapeutic target in leukemias with MLL rearrangements.
Maillard
Ivan
I
Department of Pathology, University of Michigan Medical School, 5249 Medical Sciences 1, 1301 Catherine Avenue, Ann Arbor, Michigan 48105, USA.
Hess
Jay L
JL
D000818:Animals; D006410:Hematopoiesis / Q000502:physiology*; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007938:Leukemia / Q000503:physiopathology; D046912:Multiprotein Complexes / Q000378:metabolism; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
C497422:KMT2A protein, human; C105373:MEN1 protein, human; D046912:Multiprotein Complexes; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase