BMC cancer · 2026
Prognostic significance of therapy-induced senescence and SASP dynamics in acute myeloid leukemia: a retrospective cohort study.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Ma Bing, Zhang Lihong
Аннотация
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.
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.