Tumor Treating Fields modulate apoptotic and immune programs in T-cell acute lymphoblastic leukemia cell lines.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly 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 been clinically determined in numerous solid tumors, yet their effects in hematologic malignancies remain incompletely understood. In the present study, the cellular responses of T-ALL cells to TTFields were examined. Jurkat and MOLT-4 cells were exposed to 150 kHz and 0.7 V/cm fields for up to 96 h. TTFields treatment progressively suppressed cell proliferation, induced G2/M-phase arrest, altered cell-cycle distribution, increased apoptotic fractions and increased late-apoptotic fractions. TTFields exposure also increased side-scatter intensity (indicative of increased cellular granularity or internal complexity) and MitoTracker green fluorescence in both cell lines. Intracellular ATP levels were reduced in Jurkat cells, whereas no significant change was observed in MOLT-4 cells. In parallel, transcriptional analyses revealed downregulation of CD69 and IL-2 and upregulation of RELA proto-oncogene, NF-κB subunit and CBL proto-oncogene B. Collectively, these results demonstrate that TTFields induces cytostatic and apoptotic effects accompanied by measurable structural, bioenergetic and transcriptional alterations in T-ALL cells, supporting further investigation of TTFields as a physical therapeutic approach for hematologic malignancies.