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丝氨酸蛋白酶抑制剂Kazal型2(SPINK2)在急性髓系白血病中的上调

Upregulation of SPINK2 in acute myeloid leukemia.

作者信息

Gezer Sümbül, Emrence Zeliha, Elverdi Tuğrul, Ar Muhlis Cem, Salman Yaylaz Burcu, Paçal Ferda, Ünüvar Ayşegül, Sarıman Melda, Eşkazan Ahmet Emre, Karaman Serap, Salihoğlu Ayşe, Karakaş Zeynep, Abacı Neslihan, Sırma-Ekmekci Sema

机构信息

Department of Genetics, Istanbul University, Aziz Sancar Institute of Experimental Medicine, Istanbul, Türkiye.

Istanbul University, Institute of Graduate Studies in Health Sciences, Istanbul, Türkiye.

出版信息

Adv Lab Med. 2023 Feb 20;4(1):92-104. doi: 10.1515/almed-2022-0047. eCollection 2023 Apr.

Abstract

OBJECTIVES

Acute myeloid leukemia (AML) is a highly heterogeneous disease. Although patients can be classified into risk groups based on their genetic changes, the prognosis of disease within these categories varies widely. This situation raises the need to search for new molecular markers related to AML. Serine peptidase inhibitor Kazal type 2 () has recently been reported to be upregulated in AML and associated with poor outcomes by meta-analysis and in a limited number of AML patients.

METHODS

We analyzed mRNA expression in 62 patients (45 adult and 17 pediatric) with AML and 11 cell lines using quantitative Real-Time PCR (qRT-PCR). SPINK2 protein level was determined using ELISA in cell lines.

RESULTS

We found that the expression of mRNA and protein levels in AML cell lines (HL60 and NB4) have increased compared to other cell lines (K562, Jurkat and NALM6, MCF7, HeLa, HUVEC, hFOB, 293T, U87). mRNA expression was upregulated in patients with AML compared to controls (p=0.004) and significantly lower in t(8;21)-positive patients compared to negative patients (p=0.0006).

CONCLUSIONS

Our results suggest that serves an important role in AML development. Further studies are needed to evaluate SPINK2 expression in AML patients with t(8.21) and investigate to clarify its prognostic value in various subgroups of AML.

摘要

目的

急性髓系白血病(AML)是一种高度异质性疾病。尽管患者可根据其基因变化分为不同风险组,但这些组内疾病的预后差异很大。这种情况引发了寻找与AML相关新分子标志物的需求。丝氨酸蛋白酶抑制剂Kazal型2(SPINK2)最近经荟萃分析及在少数AML患者中报道,在AML中表达上调且与不良预后相关。

方法

我们使用定量实时聚合酶链反应(qRT-PCR)分析了62例AML患者(45例成人和17例儿童)及11种细胞系中SPINK2 mRNA的表达。在细胞系中使用酶联免疫吸附测定(ELISA)确定SPINK2蛋白水平。

结果

我们发现,与其他细胞系(K562、Jurkat、NALM6、MCF7、HeLa、HUVEC、hFOB、293T、U87)相比,AML细胞系(HL60和NB4)中SPINK2 mRNA的表达及蛋白水平有所增加。与对照组相比,AML患者中SPINK2 mRNA表达上调(p = 0.004),与t(8;21)阴性患者相比,t(8;21)阳性患者中SPINK2 mRNA表达显著更低(p = 0.0006)。

结论

我们的结果表明SPINK2在AML发展中起重要作用。需要进一步研究评估t(8;21) AML患者中SPINK2的表达,并调查以阐明其在AML各亚组中的预后价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5c2/10197194/06155f1b7ebd/j_almed-2022-0047_fig_001.jpg

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