The Characterization of Acute Myeloblastic Leukemia-M2 Cell Lines with Suppressed Stromal Interaction Molecule 1 (STIM1) and its Impact on Calcium/Reactive Oxygen Species Profiles

Eman Salem Algariri ^1,2, Rabiatul Basria S. M. N. Mydin ^1*, Emmanuel Jairaj Moses ¹, Nur Arzuar Abdul Rahim ³, Narazah Mohd Yusoff ³

STIM1's potential role in promoting AML-M2 cell survival by regulating calcium/ROS interactions, as well as KRAS/MAPK and Akt-related pathways

Abstract

Introduction: Acute myeloid leukemia-M2 subtype (AML-M2) is a severe type of blood cancer that has a high rate of recurrence and death. Recent cancer research has linked stromal interaction molecule 1 (STIM1) and calcium/reactive oxygen species (ROS) interactions to cancer progression, drug resistance, and cancer cell self-renewal. However, the involvement of STIM1 in the modulation of calcium and ROS activities and AML-M2 cell survival is still unclear. Methods: The current study uses dicer-substrate siRNA (dsiRNA) knockdown of STIM1 to assess its functional activity in the AML-M2 cell line. Following STIM1 knockdown, the expression levels of genes involved in cell survival and ROS generation were measured by RT-qPCR. Calcium influx, ROS generation, cell proliferation, and colony formation were all evaluated. Results: Knocking down STIM1 exhibited a reduction in calcium influx and ROS generation. Kasumi-1 cell proliferation and colony formation were inhibited following STIM1 knockdown. Further transcriptomic profiling in this knockdown model revealed downregulation of KRAS, MAPK, C-MYC, Akt, NOX2, and PKC. Conclusion: The findings point to STIM1's potential role in promoting AML-M2 cell survival through calcium/ROS interplay-mediated control of KRAS and Akt-related pathways. Furthermore, it might recommend STIM1 and/or ROS for targeted therapy, which may contribute to regression of disease and improve the AML therapeutic strategy.

Keywords: Kasumi-1, STIM1, Acute Myeloblastic Leukemia-M2, cancer, disease

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