Case-control analysis reveals reduced caspase 3 levels in leukemia patients, indicating its potential as a therapeutic target.
Background: Caspase 3 (CASP3) is a central executioner in the apoptotic pathway, regulating essential processes including cell homeostasis, hematopoietic development, and immune regulation. Dysregulation of CASP3 has been linked to tumorigenesis in several cancers such as breast, colorectal, and uterine malignancies. In leukemia, where defective apoptosis contributes to malignant cell survival, studies assessing CASP3 expression remain scarce. Understanding its expression profile in leukemia subtypes may provide insight into disease mechanisms and potential therapeutic targets. Objective: To evaluate CASP3 gene expression in leukemia patients compared to healthy controls and to determine its association with clinical and demographic factors. Methods: A case–control study was conducted involving 112 patients diagnosed with Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), Chronic Myeloid Leukemia (CML), or Chronic Lymphocytic Leukemia (CLL), alongside age- and gender-matched healthy controls. Peripheral blood samples were collected in EDTA vacutainers, and total RNA was extracted using the Trizol method. RNA integrity was confirmed via gel electrophoresis before synthesizing complementary DNA using a High-Capacity Reverse Transcription Kit. Relative CASP3 expression was quantified using SYBR Green-based qPCR with β-actin as an internal control. Data were analyzed using the 2^-ΔΔCT method, with t-tests and ANOVA applied for statistical significance (p<0.05). Results: CASP3 expression was significantly downregulated in leukemia patients compared to controls (p=0.0012). Patients receiving chemotherapy alone demonstrated higher CASP3 levels than those undergoing combined chemoradiotherapy, although this difference did not reach statistical significance (p=0.0953). No significant associations were found with age (p=0.4616), gender (p=0.9425), or white blood cell count (p=0.4616). Conclusion: The marked reduction of CASP3 expression in leukemia supports its potential role in leukemogenesis through impaired apoptosis. These findings highlight CASP3 as a promising diagnostic biomarker and potential therapeutic target, warranting further molecular and functional investigations to explore its clinical applicability.
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Afzal et al. (2025) studied this question.
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