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探索IKZF1及其靶向微小RNA在急性淋巴细胞白血病发病机制中的作用。

Exploring the impact of IKZF1 and its targeting microRNAs in the pathogenesis of acute lymphoblastic leukemia.

作者信息

Heidari Ilia, Kariminik Ashraf

机构信息

Department of Microbiology, KeC., Islamic Azad University, Kerman, Iran.

出版信息

Ir J Med Sci. 2025 Aug 8. doi: 10.1007/s11845-025-04065-5.

Abstract

BACKGROUND

Acute lymphoblastic leukemia (ALL) is an aggressive hematologic malignancy driven by uncontrolled immature lymphoid cell proliferation. Its prognosis is significantly influenced by IKZF1 gene alterations which contribute to treatment resistance and relapse.

AIM

This study investigates the role of specific IKZF1-targeting microRNAs (e.g., hsa-miR-488, hsa-miR-4311) in ALL pathogenesis and their potential as therapeutic targets.

METHODS

Peripheral blood samples were collected from 32 ALL patients and 20 healthy controls. Total RNA and miRNAs were extracted, and cDNA was synthesized. Quantitative real-time PCR was performed to evaluate the expression of IKZF1 and the candidate miRNAs. Statistical analyses included non-parametric tests to compare expression levels between groups.

RESULTS

IKZF1 expression was significantly reduced in ALL patients compared to controls (median: 0.1160 vs. 0.8245; p = 0.002). Among the miRNAs analyzed, only hsa-miR-8085 showed a significant decrease in ALL patients (median: 0.0192 vs. 0.3411; p = 0.008). No significant differences were observed for hsa-miR-488, hsa-miR-4311, hsa-miR-6731-5p, or hsa-miR-6833-3p.

CONCLUSIONS

The significant downregulation of IKZF1 and hsa-miR-8085 in ALL patients suggests their involvement in the development of leukemia and highlights their potential as diagnostic markers or therapeutic targets.

摘要

背景

急性淋巴细胞白血病(ALL)是一种侵袭性血液系统恶性肿瘤,由未成熟淋巴细胞不受控制的增殖驱动。IKZF1基因改变对其预后有显著影响,导致治疗耐药和复发。

目的

本研究探讨特定靶向IKZF1的微小RNA(如hsa-miR-488、hsa-miR-4311)在ALL发病机制中的作用及其作为治疗靶点的潜力。

方法

收集32例ALL患者和20例健康对照者的外周血样本。提取总RNA和微小RNA,合成cDNA。进行定量实时PCR以评估IKZF1和候选微小RNA的表达。统计分析包括非参数检验以比较组间表达水平。

结果

与对照组相比,ALL患者中IKZF1表达显著降低(中位数:0.1160对0.8245;p = 0.002)。在所分析的微小RNA中,只有hsa-miR-8085在ALL患者中显著降低(中位数:0.0192对0.3411;p = 0.008)。hsa-miR-488、hsa-miR-4311、hsa-miR-6731-5p或hsa-miR-6833-3p未观察到显著差异。

结论

ALL患者中IKZF1和hsa-miR-8085的显著下调表明它们参与白血病的发生发展,并突出了它们作为诊断标志物或治疗靶点的潜力。

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