ArticleBlood advances2021
PML-controlled responses in severe congenital neutropenia with ELANE-misfolding mutations.
Article in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- The multidimensional signaling of ELANE: from congenital hematopoietic failure to immune microenvironment crosstalk and targeted interventions.Cell communication and signaling : CCS · 2026Review
- Germ line LCP1 mutations cause immunodeficiency with neutropenia, monocytopenia, lymphopenia, and defective cytokinesis.Blood advances · 2026Article
- Gingival Crevicular Fluid Proteomic Shift: From Gingivitis to Periodontitis.International dental journal · 2026Article
- Article
- A new severe congenital neutropenia syndrome associated with autosomal recessive COPZ1 mutations.Blood · 2025Article
- Cyclic neutropenia: a case report and literature review.American journal of translational research · 2025Article
- Neutrophils from patients with acquired neutropenia exhibit alterations in serine protease immunostaining and activity.British journal of haematology · 2024Article
- Truncated CSF3 receptors induce pro-inflammatory responses in severe congenital neutropenia.British journal of haematology · 2023Article
- Combination regimen of granulocyte colony-stimulating factor and recombinant human thrombopoietin improves the curative effect on elderly patients with leukemia through inducing pyroptosis and ferroptosis of leukemia cells.Cancer gene therapy · 2022Article
- Assessment of Congenital Neutropenia in Children: Common Clinical Sceneries and Clues for Management.Mediterranean journal of hematology and infectious diseases · 2022Review
- Neutrophil Elastase Defects in Congenital Neutropenia.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in ELANE cause severe congenital neutropenia (SCN), but how they affect neutrophil production and contribute to leukemia predisposition is unknown. Neutropenia is alleviated by CSF3 (granulocyte colony-stimulating factor) therapy in most cases, but dose requirements vary between patients. Here, we show that CD34+CD45+ hematopoietic progenitor cells (HPCs) derived from induced pluripotent stem cell lines from patients with SCN that have mutations in ELANE (n = 2) or HAX1 (n = 1) display elevated levels of reactive oxygen species (ROS) relative to normal iPSC-derived HPCs. In patients with ELANE mutations causing misfolding of the neutrophil elastase (NE) protein, HPCs contained elevated numbers of promyelocyte leukemia protein nuclear bodies, a hallmark of acute oxidative stress. This was confirmed in primary bone marrow cells from 3 additional patients with ELANE-mutant SCN. Apart from responding to elevated ROS levels, PML controlled the metabolic state of these ELANE-mutant HPCs as well as the expression of ELANE, suggestive of a feed-forward mechanism of disease development. Both PML deletion and correction of the ELANE mutation restored CSF3 responses of these ELANE-mutant HPCs. These findings suggest that PML plays a crucial role in the disease course of ELANE-SCN characterized by NE misfolding, with potential implications for CSF3 therapy.
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