ArticleLeukemia2013
Role of cysteine 288 in nucleophosmin cytoplasmic mutations: sensitization to toxicity induced by arsenic trioxide and bortezomib.
Article in Leukemia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Retinoic acid disrupts an NPM1c/ROS/SENP3/ARF oncogenic axis in acute myeloid leukemia.Leukemia · 2025Article
- Article
- Bortezomib suppresses acute myelogenous leukaemia stem-like KG-1a cells via NF-κB inhibition and the induction of oxidative stress.Journal of cellular and molecular medicine · 2024Article
- Mapping the Cellular Biogeography of Human Bone Marrow Niches Using Single-Cell Transcriptomics and Proteomic Imaging.bioRxiv : the preprint server for biology · 2024Article
- Article
- NPM 1 Mutations in AML-The Landscape in 2023.Cancers · 2023Review
- Targeting and Monitoring Acute Myeloid Leukaemia with Nucleophosmin-1 (International journal of molecular sciences · 2023Review
- Upregulation of osteoprotegerin inhibitsExperimental and therapeutic medicine · 2022Article
- Cystine uptake inhibition potentiates front-line therapies in acute myeloid leukemia.Leukemia · 2022Article
- Targeted therapy in NPM1-mutated AML: Knowns and unknowns.Frontiers in oncology · 2022Review
- Actinomycin D Targets NPM1c-Primed Mitochondria to Restore PML-Driven Senescence in AML Therapy.Cancer discovery · 2021Article
- NSC348884 cytotoxicity is not mediated by inhibition of nucleophosmin oligomerization.Scientific reports · 2021Article
- Nucleophosmin1 (NPM1) abnormality in hematologic malignancies, and therapeutic targeting of mutant NPM1 in acute myeloid leukemia.Therapeutic advances in hematology · 2020Review
- IncreasedOncoTargets and therapy · 2019Article
- Localization of AML-related nucleophosmin mutant depends on its subtype and is highly affected by its interaction with wild-type NPM.PloS one · 2017Article
- Potential role for all-International journal of hematologic oncology · 2016Review
- Autophagy mediates proteolysis of NPM1 and HEXIM1 and sensitivity to BET inhibition in AML cells.Oncotarget · 2016Article
- Nucleophosmin: from structure and function to disease development.BMC molecular biology · 2016Review
- Nucleophosmin Mutations Induce Chemosensitivity in THP-1 Leukemia Cells by Suppressing NF-κB Activity and Regulating Bax/Bcl-2 Expression.Journal of Cancer · 2016Article
- Spontaneous remission in three cases of AML M5 with NPM1 mutation.Clinical case reports · 2015Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in exon 12 of the nucleophosmin (NPM1) gene (NPMc+ (NPM1 COOH terminal mutations)) define a distinct subset of acute myelogenous leukemias (AMLs), in which the NPMc+ protein localizes aberrantly to the leukemic cell cytoplasm. We have found that introduction of the most common NPMc+ variant into K562 and 32D cells sensitizes these cells to apoptosis induced by drugs such as bortezomib and arsenic trioxide (ATO) that induce reactive oxygen species (ROS) formation, and that cytotoxicity is prevented in the presence of N-acetyl-L-cysteine (NAC), an ROS scavenger. The substitution of tryptophan 288 (W288) by cysteine occurs in the great majority of NPM1c+ mutations. Mutagenesis of cysteine 288 to alanine re-localizes NPMc+ from the cytoplasm to the nucleolus and attenuates the sensitivity of cells expressing this mutation to bortezomib and ATO. Primary AML cells expressing NPMc+ are also significantly more sensitive than other AML cells to apoptosis induced by both drugs at pharmacologically achievable doses. We conclude that the presence of a cysteine moiety at position 288 results in the cytoplasmic localization of NPM1c+ and the increased sensitivity to bortezomib and ATO. These data suggest that bortezomib and ATO may have increased therapeutic efficacy in NPM1c+ leukemias.
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