Tumor Treating Fields modulate apoptotic and immune programs in T‑cell acute lymphoblastic leukemia cell lines
조회 226
Background
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with limited treatment options for relapsed or refractory disease. Tumor Treating Fields (TTFields), low-intensity alternating electric fields that disrupt mitotic spindle assembly, have demonstrated clinical efficacy in various solid tumors including glioblastoma, non-small cell lung cancer, and locally advanced pancreatic cancer. However, the effects of TTFields on hematologic malignancies remain incompletely understood, highlighting the need for comprehensive investigation of electric field-based therapy in leukemic cells.
Methods
Human T-ALL cell lines (Jurkat and MOLT-4) were exposed to 150 kHz electric fields at 0.7 V/cm for 24–96 hours. Cell viability was assessed using WST-8 assay. Cell cycle distribution, apoptosis, and morphological changes were evaluated by flow cytometry. Intracellular ATP levels were measured via luminescence assay. Surface activation markers (CD69) and immune-related gene expression (CD69, IL-2, RELA, CBLB, TOX) were analyzed by flow cytometry and RT-qPCR. A non-malignant fibroblast cell line (CCD-112CoN) was used as a control to assess selectivity.
Results
TTFields exposure progressively suppressed T-ALL cell proliferation in a dose- and time-dependent manner. Flow cytometric analysis revealed reduced G1 populations, increased sub-G1 fractions, and elevated late-apoptotic (Annexin V+/PI+) populations. Side scatter intensity increased significantly, indicating enhanced intracellular granularity. MitoTracker green fluorescence was elevated in both cell lines, suggesting altered mitochondrial distribution or mass. Intracellular ATP levels decreased in Jurkat cells but remained unchanged in MOLT-4 cells. Transcriptional analysis demonstrated downregulation of CD69 and IL-2 transcripts, with marked upregulation of RELA and CBLB, particularly in Jurkat cells. TTFields had minimal effects on non-malignant CCD-112CoN cells.
Conclusions
TTFields induces cytostatic and apoptotic effects in T-ALL cells accompanied by measurable structural (increased cellular granularity), bioenergetic (ATP depletion in Jurkat), and transcriptional alterations (suppression of activation signaling, NF-κB pathway modulation). The selectivity for malignant cells over non-malignant controls suggests potential clinical applicability. These findings support further investigation of TTFields as a novel physical therapeutic modality for hematologic malignancies, with future studies warranted to elucidate underlying mechanisms and assess combination strategies with conventional chemotherapy or immunotherapy.
Published online on: May 29, 2026
Authors
- Department of Biomedical Engineering, Korea University, Seoul, Republic of Korea
Jinju Heo, Myonggeun Yoon - FieldCure Co., Ltd., Seoul, Republic of Korea
Myonggeun Yoon
