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白血病患者外周血单个核细胞中LMNA/C和胰岛素受体转录变体的差异表达

Differential Expression of LMNA/C and Insulin Receptor Transcript Variants in Peripheral Blood Mononuclear Cells of Leukemia Patients.

作者信息

Alshaalan Khalid Saud, Albawardi Turki Khalid, Zhra Mahmoud, Bin Sulaiman Norah, Jnied Osama Yaheia, Saleem Rimah Abdullah, Aljada Ahmad

机构信息

College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia.

Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia.

出版信息

J Clin Med. 2024 Apr 27;13(9):2568. doi: 10.3390/jcm13092568.

Abstract

: Recent research has identified alternative transcript variants of LMNA/C (LMNA, LMNC, LMNAΔ10, and LMNAΔ50) and insulin receptors (INSRs) as potential biomarkers for various types of cancer. The objective of this study was to assess the expression of LMNA/C and INSR transcript variants in peripheral blood mononuclear cells (PBMCs) of leukemia patients to investigate their potential as diagnostic biomarkers. : Quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) was utilized to quantify the mRNA levels of LMNA/C (LMNA, LMNC, LMNAΔ10, and LMNAΔ50) as well as INSR (IR-A and IR-B) variants in PBMCs obtained from healthy individuals (n = 32) and patients diagnosed with primary leukemias (acute myeloid leukemia (AML): n = 17; acute lymphoblastic leukemia (ALL): n = 8; chronic myeloid leukemia (CML): n = 5; and chronic lymphocytic leukemia (CLL): n = 15). : Only LMNA and LMNC transcripts were notably present in PBMCs. Both exhibited significantly decreased expression levels in leukemia patients compared to the healthy control group. Particularly, the LMNC:LMNA ratio was notably higher in AML patients. Interestingly, IR-B expression was not detectable in any of the PBMC samples, precluding the calculation of the IR-A:IR-B ratio as a diagnostic marker. Despite reduced expression across all types of leukemia, IR-A levels remained detectable, indicating its potential involvement in disease progression. : This study highlights the distinct expression patterns of LMNA/C and INSR transcript variants in PBMCs of leukemia patients. The LMNC:LMNA ratio shows promise as a potential diagnostic indicator for AML, while further research is necessary to understand the role of IR-A in leukemia pathogenesis and its potential as a therapeutic target.

摘要

最近的研究已确定核纤层蛋白A/C(LMNA/C,包括LMNA、LMNC、LMNAΔ10和LMNAΔ50)和胰岛素受体(INSRs)的可变转录本变体是各类癌症的潜在生物标志物。本研究的目的是评估白血病患者外周血单个核细胞(PBMCs)中LMNA/C和INSR转录本变体的表达情况,以研究其作为诊断生物标志物的潜力。:采用定量逆转录聚合酶链反应(RT-qPCR)来定量健康个体(n = 32)以及被诊断为原发性白血病(急性髓系白血病(AML):n = 17;急性淋巴细胞白血病(ALL):n = 8;慢性髓系白血病(CML):n = 5;慢性淋巴细胞白血病(CLL):n = 15)的患者的PBMCs中LMNA/C(LMNA、LMNC、LMNAΔ10和LMNAΔ50)以及INSR(IR-A和IR-B)变体的mRNA水平。:只有LMNA和LMNC转录本在PBMCs中显著存在。与健康对照组相比,二者在白血病患者中的表达水平均显著降低。特别是,AML患者中LMNC:LMNA的比值显著更高。有趣的是,在任何PBMC样本中均未检测到IR-B的表达,因此无法计算IR-A:IR-B比值作为诊断标志物。尽管在所有类型的白血病中表达均降低,但IR-A水平仍可检测到,表明其可能参与疾病进展。:本研究突出了白血病患者PBMCs中LMNA/C和INSR转录本变体的独特表达模式。LMNC:LMNA比值有望成为AML的潜在诊断指标,而需要进一步研究以了解IR-A在白血病发病机制中的作用及其作为治疗靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3628/11084221/211f2f45384a/jcm-13-02568-g001.jpg

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