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Abstract

The erythropoietic dysfunction and iron insufficiency associated with β -Thalassemia (β -TH) underscore the importance of augmenting traditional diagnostic techniques with independent biomarkers, beyond standard panels. This single-center case–control study (n = 120 β -TH major, 55; β -TH intermedia, 25; control, 40) examined whether circulating phosphatidylinositol-3-kinase (PI3K) distinguishes patients from controls and correlates with hemoglobin fractions. The serum PI3K was significantly higher in β -TH (p < 0.001), with excellent discrimination tested in serum (AUC = 0.934; optimal cut-off > 1301 pg/mL; sensitivity 100%, specificity 80%). In a multivariable model, HbA2% and HbF% were both positively and independently associated with PI3K. These results are biologically consistent with the interaction of erythroid stress, iron homeostasis, and PI3K–AKT signaling, and suggest that PI3K provides unique and complementary diagnostic value in parallel with traditional markers. While human serum circulating PI3K in β -TH data with formal diagnostic parameters are quite scarce. These results suggest that PI3K may serve as a non-invasive complementary biomarker and support multi-center, longitudinal validation with cut-offs confirmation, temporal responsiveness around transfusion/chelation, and supplemental clinical utility in prediction models. Any therapeutic implications targeting the PI3K pathway remain exploratory and require disease-specific studies.

Keywords

Beta-thalassemia, Biomarker, Hemoglobin, Iron overload, Phosphatidylinositol 3-kinase, Thalassemia intermedia, Thalassemia major

Subject Area

Chemistry

Article Type

Article

First Page

1820

Last Page

1826

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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