芦可替尼通过负调节剂对骨髓增殖性肿瘤的影响。

Effects of Ruxolitinib on Myeloproliferative Neoplasms via the Negative Regulators.

出版信息

Clin Lab. 2023 Feb 1;69(2). doi: 10.7754/Clin.Lab.2022.220442.

DOI:10.7754/Clin.Lab.2022.220442

Abstract

BACKGROUND

We evaluated the JAK2V617F mutation and p-JAK2, SOCS-1, SHP-1 expression in JAK2V617F positive myeloproliferative neoplasms (MPNs) patients and the role of JAK/STAT pathway in human erythroleukemia (HEL) cells, which had JAK2V617F mutation.

METHODS

Protein expression of p-JAK2, SOCS-1, SHP-1 in bone marrow biopsies (BMBs) were detected by immunohistochemical staining methods. Cell apoptosis and cell cycle were detected by flow cytometry and Caspase 3/7 assay kits.

RESULTS

The p-JAK2, SOCS-1, and SHP-1 expressions were significantly different between JAK2V617F positive MPN and control patients (p < 0.01); 2. After being treated for 3 months, the p-JAK2, SOCS-1, and SHP-1 expressions were significantly different compared with newly diagnosed patients (p < 0.01). 3. HEL cell viabilities were significantly different after being treated with different concentrations of ruxolitinib. Ruxolitinib had a significant effect on the cell apoptosis, viability, and the protein activity of caspase-3 and -7 of HEL cells. 3. The mRNA and protein expressions of JAK2 and the protein expression of p-JAK2 were gradually decreased (p ＜ 0.01, p ＜ 0.05), while the mRNA and protein expressions of SOCS1 and SHP1 were gradually increased (all p ＜ 0.01).

摘要

背景

我们评估了 JAK2V617F 突变和 p-JAK2、SOCS-1、SHP-1 在 JAK2V617F 阳性骨髓增殖性肿瘤（MPN）患者中的表达，以及 JAK/STAT 通路在具有 JAK2V617F 突变的人红白血病（HEL）细胞中的作用。

方法

采用免疫组织化学染色法检测骨髓活检（BMB）中 p-JAK2、SOCS-1、SHP-1 的蛋白表达。通过流式细胞术和 Caspase 3/7 检测试剂盒检测细胞凋亡和细胞周期。

结果

JAK2V617F 阳性 MPN 与对照患者之间的 p-JAK2、SOCS-1 和 SHP-1 表达存在显著差异（p＜0.01）；2. 治疗 3 个月后，与初诊患者相比，p-JAK2、SOCS-1 和 SHP-1 的表达存在显著差异（p＜0.01）。3. 不同浓度的芦可替尼处理后，HEL 细胞活力存在显著差异。芦可替尼对 HEL 细胞的细胞凋亡、活力以及 caspase-3 和 -7 的蛋白活性有显著影响。3. JAK2 的 mRNA 和蛋白表达以及 p-JAK2 的蛋白表达逐渐降低（p＜0.01，p＜0.05），而 SOCS1 和 SHP1 的 mRNA 和蛋白表达逐渐增加（均 p＜0.01）。