The Role of HSP70 in Leukemia: A Systematic Review and Meta-Analysis Investigating Its Potential as a Biomarker Through Expression Differences and Hematological Associations

Background: Leukemia is a major cause of cancer-related morbidity and mortality, representing the most common childhood malignancy and remaining associated with poor outcomes and relapse in adult acute subtypes. Despite therapeutic progress in leukemia management, survival outcomes remain poor, highlighting the urgent need for reliable biomarkers and novel therapeutic targets. Heat shock protein 70 (HSP70), a molecular chaperone central to protein folding, apoptosis regulation, and oncogenic signalling, has been increasingly implicated in leukemogenesis and therapy resistance. However, the clinical utility of HSP70 remains uncertain due to small cohorts and methodological heterogeneity across studies. This systematic review and meta-analysis provides a quantitative evaluation of HSP70 expression in leukemia and explores its potential as a diagnostic, prognostic, and therapeutic biomarker. Methods: A systematic review was conducted in accordance with PRISMA guidelines. EBSCO, PubMed, ProQuest, ScienceDirect, and Scopus were searched for studies reporting quantitative HSP70 expression in leukemia and healthy controls. Eligible studies met predefined inclusion and exclusion criteria. Data were pooled using a random-effects model, with effect sizes calculated as standardised mean differences (Cohen’s d), and statistical analyses performed in IBM SPSS Statistics (v28.0). Results: After applying eligibility criteria, data from 261 leukemia patients and 214 healthy controls across three studies (four datasets) were included. Pooled analysis demonstrated significantly elevated HSP70 expression in leukemia patients compared with controls (Cohen’s d = 1.498, 95% CI: 1.279 - 1.717, p < 0.001), representing a large effect size. No heterogeneity was observed (I² = 0%). The study was prospectively registered with PROSPERO (CRD420251019261). Conclusion: This meta-analysis demonstrates consistent overexpression of HSP70 in leukemia, supporting its potential as a diagnostic, prognostic, and therapeutic biomarker, while highlighting the need for further clinical validation.