ArticleCell death discovery2022
Targeting matrix metallopeptidase 2 by hydroxyurea selectively kills acute myeloid mixed-lineage leukemia.
Article in Cell death discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- Hydroxyurea induces an oxidative stress response that triggers ER expansion and cytoplasmic protein aggregation.PLoS biology · 2025Article
- Integration of scRNA-seq and ST-seq identifies hyperproliferative RRM2+ cells features and therapeutic targets in gastric cancer.Journal of translational medicine · 2025Article
- Identification of mitochondrial ATP synthase as the cellular target of Ru-polypyridyl-National science review · 2024Article
- Targeting cytohesin-1 suppresses acute myeloid leukemia progression and overcomes resistance to ABT-199.Acta pharmacologica Sinica · 2024Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Oncogene-induced tumorigenesis results in the variation of epigenetic modifications, and in addition to promoting cell immortalization, cancer cells undergo more intense cellular stress than normal cells and depend on other support genes for survival. Chromosomal translocations of mixed-lineage leukemia (MLL) induce aggressive leukemias with an inferior prognosis. Unfortunately, most MLL-rearranged (MLL-r) leukemias are resistant to conventional chemotherapies. Here, we showed that hydroxyurea (HU) could kill MLL-r acute myeloid leukemia (AML) cells through the necroptosis process. HU target these cells by matrix metallopeptidase 2 (MMP2) deficiency rather than subordinate ribonucleotide reductase regulatory subunit M2 (RRM2) inhibition, where MLL directly regulates MMP2 expression and is decreased in most MLL-r AMLs. Moreover, iron chelation of HU is also indispensable for inducing cell stress, and MMP2 is the support factor to protect cells from death. Our preliminary study indicates that MMP2 might play a role in the nonsense-mediated mRNA decay pathway that prevents activation of unfolding protein response under innocuous endoplasmic reticulum stress. Hence, these results reveal a possible strategy of HU application in MLL-r AML treatment and shed new light upon HU repurposing.
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Registered trials
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