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JAK2 as Predictor of Therapeutic Response in Patients with Chronic Myeloid Leukemia Treated with Imatinib
Disease Markers ( IF 3.464 ) Pub Date : 2024-4-12 , DOI: 10.1155/2024/2906566
Indra Wijaya 1 , Muhammad H. Bashari 2 , Lelani Reniarti 3 , Anita Rahmawati 1 , Rully M. A. Roesli 4
Affiliation  

Background. Chronic myeloid leukemia (CML) or chronic granulocytic leukemia is a myeloproliferative neoplasm indicated by the presence of the Philadelphia (Ph+) chromosome. First-line tyrosine kinase inhibitor, imatinib, is the gold standard for treatment. However, there has been known unresponsiveness to treatment, especially due to the involvement of other genes, such as the Janus kinase 2 (JAK2) gene. This study aimed to evaluate the relationships between JAK2 levels and complete hematological response (CHR), as well as early molecular response (EMR) after 3 months of imatinib treatment in patients with chronic phase CML. Methods. Patients with Ph+ CML in the chronic phase (n = 40; mean age, 40 ± 11 years) were recruited to complete assessments consisting of clinical examination and blood test, including evaluation of complete blood counts and the JAK2 levels, at baseline and following 3 months of therapy with imatinib (at an oral dose of 400 mg per day). Subjects were divided into two groups according to the presence of CHR and EMR. Results. JAK2 gene levels, phosphorylated, and total JAK2 proteins at baseline were significantly lower in the group with the presence of CHR and EMR. In addition, baseline JAK2 levels, including JAK2 gene expression, phosphorylated, and total JAK2 proteins, were negatively correlated with the presence of CHR and EMR. Conclusions. Based on these findings, JAK2 levels may be a potential indicator for evaluating treatment response on imatinib due to its role in the pathophysiology of CML.

中文翻译:

JAK2 作为伊马替尼治疗慢性粒细胞白血病患者治疗反应的预测因子

背景。慢性粒细胞白血病 (CML) 或慢性粒细胞白血病是一种骨髓增生性肿瘤,表现为费城 (Ph+) 染色体的存在。一线酪氨酸激酶抑制剂伊马替尼是治疗的金标准。然而,已知治疗无反应,特别是由于其他基因的参与,例如 Janus 激酶 2 (JAK2) 基因。本研究旨在评估慢性期 CML 患者伊马替尼治疗 3 个月后 JAK2 水平与完全血液学反应 (CHR) 以及早期分子反应 (EMR) 之间的关系。方法。招募慢性期 Ph+ CML 患者(n  = 40;平均年龄,40 ± 11 岁)来完成包括临床检查和血液检测在内的评估,包括基线时和 3 年后的全血细胞计数和 JAK2 水平评估。伊马替尼治疗数月(每天口服 400 毫克)。根据 CHR 和 EMR 的存在,受试者被分为两组。结果。在存在 CHR 和 EMR 的组中,基线时的 JAK2 基因水平、磷酸化和总 JAK2 蛋白显着较低。此外,基线 JAK2 水平,包括 JAK2 基因表达、磷酸化和总 JAK2 蛋白,与 CHR 和 EMR 的存在呈负相关。结论。基于这些发现,由于 JAK2 在 CML 病理生理学中的作用,JAK2 水平可能成为评估伊马替尼治疗反应的潜在指标。
更新日期:2024-04-12
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