Involvement of ORAI1/SOCE in Human AML Cell Lines and Primary Cells According to ABCB1 Activity, LSC Compartment and Potential Resistance to Ara-C Exposure

International Journal of Molecular Sciences

Aurélie Guillemette¹  Sofia Titah¹  Ossama Labiad¹  Bruno Quesnel¹  Pauline Peyrouze¹  Céline Berthon¹  Yasmine Touil¹  Clara Lewuillon¹  Marie-Océane Laguillaumie¹  Meyling Cheok¹  Thierry Idziorek¹  Adeline Barthélémy¹  Loïc Lemonnier²  Valerio Farfarellio²  Faruk Azam Shaik³  Mehmet Cagatay Tarhan⁴  Nathalie Jouy⁵ 

[1] CNRS, Inserm, CHU Lille, UMR 9020, UMR-S 1277—Canther—Cancer Heterogeneity, Plasticity and Resistance to Therapies, Université de Lille, F-59000 Lille, France;Inserm, U1003-PHYCEL-Physiologie Cellulaire, Université de Lille, F-59000 Lille, France;Institut de Recherche sur le Cancer de Lille (IRCL), F-59000 Lille, France;LIMMS/CNRS-IIS IRL2820, The University of Tokyo, Tokyo 153-8505, Japan;UMS 2014/US41 Plateformes Lilloises En Biologie Et Sante, Université de Lille, F-59000 Lille, France;

关键词: calcium;    SOCE;    AML;    ORAI1;    ABCB1;    leukemic stem cells;   

DOI  :  10.3390/ijms23105555

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown