Spleen Tyrosine Kinase in Malignancies and Sepsis: Pathophysiological Roles and Biomarker Potential—A Narrative Review

Spleen tyrosine kinase is a non-receptor tyrosine kinase that couples receptor engagement to cellular survival, immune responses, and tissue injury. This narrative review compares its biology in malignancies and sepsis to examine how cellular compartment, receptor architecture, activation state, and signaling duration alter the meaning of a common signaling hub. A structured narrative search of PubMed/MEDLINE, Scopus, and Web of Science covered English-language publications from January 2000 to August 2026, supplemented by older seminal studies. In several hematological malignancies, sustained receptor signaling or oncogenic cooperation supports malignant-cell persistence; solid tumors show both tumor-promoting and tumor-suppressive functions. In sepsis, dynamically changing immune and vascular responses link spleen tyrosine kinase to pathogen recognition, inflammatory and oxidative responses, endothelial dysfunction, and organ injury. Oncology includes mechanistic studies, human cohorts, and early clinical therapeutic trials, whereas sepsis evidence remains predominantly experimental, with limited human observational and ex vivo validation. Transcript abundance, total protein, and phosphorylation are distinct biomarker endpoints whose interpretation requires identification of the cellular source and sampling context. Kinase inhibitors have shown clinical activity in selected malignancies and protection in experimental sepsis, but these findings do not establish a validated predictive biomarker or clinical efficacy in sepsis. Translation requires disease-specific validation, standardized cellular assessment, and attention to treatment timing and preservation of host defense.