The role of menin in hematopoiesis

Abstract

In the hematopoietic system, menin wasfound to interact with MLL, a largeprotein encoded by the mixedlinageleukemiagenethat actsasa histone H3 merhyltransferase.The MLL gene is a recurrent target for translocations in both acute myeloidand acute lymphoid leukemias. MLL gene rearrangementsinvolvea varietyoftranslocation partners, givingrise 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 essentialparmer of MLL fusion proteins in leukemiccellsand that it regulatesnormal hematopoiesis. In the absence of menin, steady-state hematopoiesisislargely preserved; however, menin-deficienr hematopoietic stem cellsaremarkedlydeficientin situationsofhematopoietic stress, such asduring recoveryafter bone marrow transplantation. In leukemias driven by MLL fusion proteins, menin is essential for transformation and growth ofthe malignant cells. Thus, menin-Ml.L interactions represent a promising therapeutic target in leukemiaswith MLL rearrangements. © 2009 Landes Bioscience and Springer Science+Business Media.