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Updated: Jun 12, 2026
Simultaneous Imaging and Flow-Cytometry-based Detection of Multiple Fluorescent Senescence Markers in Therapy-Induced Senescent Cancer Cells
Published on: July 12, 2022
Prognostic significance of therapy-induced senescence and SASP dynamics in acute myeloid leukemia: a retrospective
1Department of Hematology, The First Hospital of Hebei Medical University, No. 89 Donggang Road, Shijiazhuang City, Hebei Province, 050031, China. malishuqing@sina.com.
Background:
Chemotherapy constitutes the backbone of Acute Myeloid Leukemia (AML) treatment but often induces cellular senescence. While senescence initially halts tumor proliferation, the accumulation of senescent cells and the Senescence-Associated Secretory Phenotype (SASP) may promote leukemic survival and relapse. The clinical correlation between post-treatment senescence burden and AML prognosis remains poorly characterized.
Methods:
We conducted a single-center retrospective study analyzing 128 newly diagnosed AML patients treated with standard induction chemotherapy between January 2019 and December 2023. Bone marrow samples were assessed at diagnosis and post-induction. Senescent cell burden was quantified via p16INK4a and p21Cip1 expression, alongside Senescence-Associated β-galactosidase (SA-β-gal) activity using flow cytometry. Immune sub-clustering was performed to evaluate senescence in progenitor versus mature populations. SASP factors (IL-6, IL-8, TNF-α) were measured in bone marrow plasma by ELISA. Patients were stratified into High-Senescence and Low-Senescence groups based on median cut-off values.
Results:
Induction chemotherapy significantly increased the proportion of senescent cells and normalized SASP levels compared to baseline (P < 0.001), with LSC progenitors exhibiting the highest senescence burden. High post-induction senescence burden was positively correlated with adverse cytogenetics and minimal residual disease (MRD) positivity. Senescence markers strongly correlated with IL-6 and IL-8, but not TNF-α. Patients in the High-Senescence group exhibited significantly inferior Event-Free Survival (median EFS: 8.5 vs. 18.2 months, P = 0.002) and Overall Survival (median OS: 14.2 vs. 26.5 months, P = 0.004). Multivariate Cox regression identified high IL-6 levels (HR 2.14, 95% CI 1.32-3.48) and elevated p16INK4a (HR 1.98, 95% CI 1.15-3.40) as independent predictors of poor prognosis.
Conclusion:
Therapy-induced senescence creates a pro-tumoral microenvironment via SASP in AML. High senescence burden post-induction is a robust biomarker for poor outcomes, suggesting that senolytic strategies targeting these cells could improve therapeutic efficacy.
