ELANE, encoding neutrophil elastase, is closely associated with neutrophil-related biological functions. It is involved in neutrophil maturation, and its abnormal function can lead to various neutrophil-related disorders. Mutations in ELANE are often associated with severe congenital neutropenia (CN), a pre-leukemia bone marrow failure syndrome [1,4,5,6,7].

ELANE-CN patients can be treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF), but some do not respond, and about 15% may develop myelodysplasia or acute myeloid leukemia [1]. CRISPR-Cas9n-mediated editing of the ELANE promoter has shown promise in restoring defective neutrophil differentiation of ELANE-CN CD34+ hematopoietic stem and progenitor cells (HSPCs) both in vitro and in vivo, without affecting edited neutrophil functions, suggesting a potential gene therapy approach [1]. In gastric cancer, ELANE is significantly up-regulated, and its expression levels affect patient survival. High ELANE expression is related to poor prognosis, and it may participate in pyroptosis and immune infiltration in gastric cancer, making it a promising prognostic biomarker [2]. Also, human neutrophils release catalytically active ELANE to selectively kill many cancer cell types while sparing non-cancer cells, raising the possibility of developing it as a broad anti-cancer therapy [3].

In conclusion, ELANE is crucial for neutrophil-related functions. Studies on ELANE-associated neutropenia and its role in cancer, such as gastric cancer, through various experimental models, including gene-editing techniques in HSPCs, have provided insights into its functions in disease. These findings may help develop new therapeutic strategies for neutrophil-related disorders and certain cancers.

References:

1. Nasri, Masoud, Ritter, Malte U, Mir, Perihan, Welte, Karl, Skokowa, Julia. 2024. CRISPR-Cas9n-mediated ELANE promoter editing for gene therapy of severe congenital neutropenia. In Molecular therapy : the journal of the American Society of Gene Therapy, 32, 1628-1642. doi:10.1016/j.ymthe.2024.03.037. https://pubmed.ncbi.nlm.nih.gov/38556793/

2. Cui, Ming, Wang, Xiaowu, Qiao, Haiyan, Wu, Shixi, Shang, Bingbing. 2024. ELANE is a promising prognostic biomarker that mediates pyroptosis in gastric cancer. In Heliyon, 10, e34360. doi:10.1016/j.heliyon.2024.e34360. https://pubmed.ncbi.nlm.nih.gov/39130462/

3. Cui, Chang, Chakraborty, Kasturi, Tang, Xu Anna, Greene, Geoffrey, Becker, Lev. 2021. Neutrophil elastase selectively kills cancer cells and attenuates tumorigenesis. In Cell, 184, 3163-3177.e21. doi:10.1016/j.cell.2021.04.016. https://pubmed.ncbi.nlm.nih.gov/33964209/

4. Makaryan, Vahagn, Zeidler, Cornelia, Bolyard, Audrey Anna, Welte, Karl, Dale, David C. . The diversity of mutations and clinical outcomes for ELANE-associated neutropenia. In Current opinion in hematology, 22, 3-11. doi:10.1097/MOH.0000000000000105. https://pubmed.ncbi.nlm.nih.gov/25427142/

5. Skokowa, Julia, Dale, David C, Touw, Ivo P, Zeidler, Cornelia, Welte, Karl. 2017. Severe congenital neutropenias. In Nature reviews. Disease primers, 3, 17032. doi:10.1038/nrdp.2017.32. https://pubmed.ncbi.nlm.nih.gov/28593997/

6. Rao, Shuquan, Yao, Yao, Soares de Brito, Josias, Newburger, Peter E, Bauer, Daniel E. 2021. Dissecting ELANE neutropenia pathogenicity by human HSC gene editing. In Cell stem cell, 28, 833-845.e5. doi:10.1016/j.stem.2020.12.015. https://pubmed.ncbi.nlm.nih.gov/33513358/

7. Wang, Jing, Zhang, Haitao, Wang, Yu, Liang, Lei, Yang, Zeyu. . Severe congenital neutropenia caused by ELANE gene mutation: A case report and literature review. In Medicine, 101, e31357. doi:10.1097/MD.0000000000031357. https://pubmed.ncbi.nlm.nih.gov/36343040/