Menin is necessary for long term maintenance of meningioma-1 driven leukemia.
Menin is necessary for long term maintenance of meningioma-1 driven leukemia.
复制标题
DOI：
10.1038/s41375-021-01146-z
复制
发表时间：
2021-05
期刊：
影响因子：
11.4
通讯作者：
Bernt KM
中科院分区：
文献类型：
--
作者：
Libbrecht C;Xie HM;Kingsley MC;Haladyna JN;Riedel SS;Alikarami F;Lenard A;McGeehan GM;Ernst P;Bernt KM
Translocations of Meningioma-1 (MN1) occur in a subset of acute myeloid leukemias (AML) and result in high expression of MN1, either as a full-length protein, or as a fusion protein that includes most of the N-terminus of MN1. High levels of MN1 correlate with poor prognosis. When overexpressed in murine hematopoietic progenitors, MN1 causes an aggressive AML characterized by an aberrant myeloid precursor-like gene expression program that shares features of KMT2A-rearranged (KMT2A-r) leukemia, including high levels of Hoxa and Meis1 gene expression. Compounds that target a critical KMT2A–Menin interaction have proven effective in KMT2A-r leukemia. Here, we demonstrate that Menin (Men1) is also critical for the self-renewal of MN1-driven AML through the maintenance of a distinct gene expression program. Genetic inactivation of Men1 led to a decrease in the number of functional leukemia-initiating cells. Pharmacologic inhibition of the KMT2A–Menin interaction decreased colony-forming activity, induced differentiation programs in MN1-driven murine leukemia and decreased leukemic burden in a human AML xenograft carrying an MN1-ETV6 translocation. Collectively, these results nominate Menin inhibition as a promising therapeutic strategy in MN1-driven leukemia.
登录
查看更多内容
影响因子：
7.3
作者：
Borkin D;Klossowski S;Pollock J;Miao H;Linhares BM;Kempinska K;Jin Z;Purohit T;Wen B;He M;Sun D;Cierpicki T;Grembecka J
通讯作者：
Grembecka J
影响因子：
11.4
作者：
Carella, C.;Bonten, J.;Grosveld, G. C.
通讯作者：
Grosveld, G. C.
影响因子：
16
作者：
Hughes, CM;Rozenblatt-Rosen, O;Meyerson, M
通讯作者：
Meyerson, M
影响因子：
28.2
作者：
Kühn MW;Song E;Feng Z;Sinha A;Chen CW;Deshpande AJ;Cusan M;Farnoud N;Mupo A;Grove C;Koche R;Bradner JE;de Stanchina E;Vassiliou GS;Hoshii T;Armstrong SA
通讯作者：
Armstrong SA
影响因子：
50.3
作者：
Heuser, Michael;Yun, Haiyang;Humphries, R. Keith
通讯作者：
Humphries, R. Keith