期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 23, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/ijms23105555
关键词
calcium; SOCE; AML; ORAI1; ABCB1; leukemic stem cells; NFAT; Ara-C
资金
- Contrat de Plan Etat-Region CPER Cancer
- INSERM
- CNRS
- Ligue contre le cancer (Septentrion)
- Ligue nationale contre le cancer
- Fondation ARC
- University of Lille
- Institut de Recherche sur le Cancer de Lille (IRCL)
- Lille Hospital
- Hauts de France Region
This study reveals the importance of ORAI1/SOCE in AML, not only showing the association in cell lines but also confirming it in primary cells isolated from patients. Additionally, we found that SOCE varies according to differentiation status, ABCB1 activity level, and LSC proportion in these models.
Acute myeloid leukemia (AML) is a hematological malignancy with a high risk of relapse. This issue is associated with the development of mechanisms leading to drug resistance that are not yet fully understood. In this context, we previously showed the clinical significance of the ATP binding cassette subfamily B-member 1 (ABCB1) in AML patients, namely its association with stemness markers and an overall worth prognosis. Calcium signaling dysregulations affect numerous cellular functions and are associated with the development of the hallmarks of cancer. However, in AML, calcium-dependent signaling pathways remain poorly investigated. With this study, we show the involvement of the ORAI1 calcium channel in store-operated calcium entry (SOCE), the main calcium entry pathway in non-excitable cells, in two representative human AML cell lines (KG1 and U937) and in primary cells isolated from patients. Moreover, our data suggest that in these models, SOCE varies according to the differentiation status, ABCB1 activity level and leukemic stem cell (LSC) proportion. Finally, we present evidence that ORAI1 expression and SOCE amplitude are modulated during the establishment of an apoptosis resistance phenotype elicited by the chemotherapeutic drug Ara-C. Our results therefore suggest ORAI1/SOCE as potential markers of AML progression and drug resistance apparition.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据