Journal article
Clara Libbrecht, H. Xie, Molly C. Kingsley, Jessica N Haladyna, Simone S. Riedel, Fatemeh Alikarami, Alexandra Lenard, G. McGeehan, P. Ernst, K. Bernt
Leukemia, 2021
Leukemia, 2021
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APA
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Libbrecht, C., Xie, H., Kingsley, M. C., Haladyna, J. N., Riedel, S. S., Alikarami, F., … Bernt, K. (2021). Menin is necessary for long term maintenance of meningioma-1 driven leukemia. Leukemia.
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Libbrecht, Clara, H. Xie, Molly C. Kingsley, Jessica N Haladyna, Simone S. Riedel, Fatemeh Alikarami, Alexandra Lenard, G. McGeehan, P. Ernst, and K. Bernt. “Menin Is Necessary for Long Term Maintenance of Meningioma-1 Driven Leukemia.” Leukemia (2021).
MLA
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Libbrecht, Clara, et al. “Menin Is Necessary for Long Term Maintenance of Meningioma-1 Driven Leukemia.” Leukemia, 2021.
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@article{clara2021a,
title = {Menin is necessary for long term maintenance of meningioma-1 driven leukemia},
year = {2021},
journal = {Leukemia},
author = {Libbrecht, Clara and Xie, H. and Kingsley, Molly C. and Haladyna, Jessica N and Riedel, Simone S. and Alikarami, Fatemeh and Lenard, Alexandra and McGeehan, G. and Ernst, P. and Bernt, K.}
}
Abstract
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.