Department of Pathology, University of Michigan Medical School, 5249 Medical Sciences 1, 1301 Catherine Avenue, Ann Arbor, Michigan 48105, USA.
Adv Exp Med Biol. 2009;668:51-7. doi: 10.1007/978-1-4419-1664-8_5.
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.
在造血系统中，发现 menin 与 MLL 相互作用，MLL 是混合谱系白血病基因编码的一种大型蛋白质，作为组蛋白 H3 甲基转移酶发挥作用。MLL 基因是急性髓系白血病和急性淋巴细胞白血病中易位的反复靶点。MLL 基因重排涉及多种易位伙伴，导致 MLL 融合蛋白的转化能力通过上调同源盒 (Hox) 基因以及其他靶基因的表达来介导。最近的研究表明，menin 是白血病细胞中 MLL 融合蛋白的必需伴侣，它调节正常造血。在没有 menin 的情况下，稳态造血基本得到保留；然而，menin 缺陷的造血干细胞在造血应激情况下（如骨髓移植后恢复期间）明显缺乏。在由 MLL 融合蛋白驱动的白血病中，menin 对于恶性细胞的转化和生长是必需的。因此，menin-MLL 相互作用是 MLL 重排白血病有前途的治疗靶点。
