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伊马替尼与羟基脲联合治疗对慢性髓性白血病(CML)患者血液学参数及基因表达的影响研究

Investigation of the Effect of Imatinib and Hydroxyurea Combination Therapy on Hematological Parameters and Gene Expression in Chronic Myeloid Leukemia (CML) Patients.

作者信息

Al-Amleh Esraa K, Al-Sanabra Ola M, Alqaisi Khalid M, Alqaraleh Moath, Al-Nahal Jumana, Hamadneh Lama, Malki Mohammed Imad, Alhmoud Jehad F

机构信息

Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan.

Pharmacological and Diagnostic Research Center (PDRC), Al-Ahliyya Amman University, Amman 19328, Jordan.

出版信息

J Clin Med. 2022 Aug 24;11(17):4954. doi: 10.3390/jcm11174954.

DOI:10.3390/jcm11174954
PMID:36078884
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9456239/
Abstract

(1) Background: Chronic myeloid leukemia is defined as the neoplastic development of mostly myeloid cells in the bone marrow. Several treatments, including chemotherapy, radiation, hormone treatment, and immunological therapy, can be used to control this condition. The therapeutic impact on leukemic individuals varies, and the response to therapy varies between patients due to disease heterogeneity. The primary goal of this study is to compare the effects of single and Imatinib (IM) and Hydroxyurea (HU) combined treatment on hematological parameters and gene expression in CML patients. (2) Methods: This study was conducted on 51 patients, with chronic myeloid leukemia, who were admitted to Al-Basher hospital in Amman, Jordan, for follow-up. Their hematological parameters were checked and gene expression was measured for (BCL2, PP2A, CIP2A, and WT1). (3) Results: The BCL2 gene was found to be less expressed in both IM and (HU + IM) treatments as compared to the HU group alone, while PP2A gene expression was raised. Such a thing indicates that the outcome of the combined therapy method is not ideal, since PP2A activation causes CML cells to move toward the blast crisis stage. Furthermore, CIP2A gene expression revealed that IM and (HU + IM) had the same therapeutic effect and were more successful in CML patients than HU alone. With regards to the treatment effect on hematological parameters, notably in CML patients in later stages, the combination therapy (HU + IM) raised lymphocyte count, indicating a greater response to the treatment. When compared to single medicines, the combination treatment reduced the proportion of neutrophils to normal reference ranges. Platelet counts, on the other hand, dramatically decreased in both IM and (HU + IM). (4) Conclusion: Because the studied genes (BCL2, PP2A, CIP2A, and WT1) are participating in cell proliferation and death, the findings show that the examined genes are significant to understand the efficacy of various therapies. Furthermore, it was found that there was a clear effect of the clinic-based strategic treatment on hematological indicators such as WBCs, lymphocytes, neutrophils, and platelet counts.

摘要

(1) 背景:慢性髓性白血病被定义为骨髓中大多髓系细胞的肿瘤性发展。包括化疗、放疗、激素治疗和免疫治疗在内的多种治疗方法可用于控制这种疾病。对白血病个体的治疗效果各不相同,由于疾病异质性,患者对治疗的反应也存在差异。本研究的主要目的是比较单药以及伊马替尼(IM)与羟基脲(HU)联合治疗对慢性髓性白血病患者血液学参数和基因表达的影响。(2) 方法:本研究对51例慢性髓性白血病患者进行,这些患者被收治于约旦安曼的阿尔 - 巴舍尔医院进行随访。检查了他们的血液学参数,并测量了(BCL2、PP2A、CIP2A和WT1)的基因表达。(3) 结果:与单独使用HU组相比,在IM和(HU + IM)治疗中均发现BCL2基因表达较低,而PP2A基因表达升高。这表明联合治疗方法的结果并不理想,因为PP2A激活会使慢性髓性白血病细胞走向急变期。此外,CIP2A基因表达显示IM和(HU + IM)具有相同的治疗效果,并且在慢性髓性白血病患者中比单独使用HU更成功。关于对血液学参数的治疗效果,特别是在晚期慢性髓性白血病患者中,联合治疗(HU + IM)提高了淋巴细胞计数,表明对治疗的反应更大。与单一药物相比,联合治疗使中性粒细胞比例降至正常参考范围。另一方面,在IM和(HU + IM)中血小板计数均显著下降。(4) 结论:由于所研究的基因(BCL2、PP2A、CIP2A和WT1)参与细胞增殖和死亡,研究结果表明所研究的基因对于理解各种治疗的疗效具有重要意义。此外,还发现基于临床的策略性治疗对白细胞、淋巴细胞、中性粒细胞和血小板计数等血液学指标有明显影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/982c/9456239/a2d60c4fc4b5/jcm-11-04954-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/982c/9456239/d5f69770a125/jcm-11-04954-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/982c/9456239/dc82396fa6a8/jcm-11-04954-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/982c/9456239/f7d461d76055/jcm-11-04954-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/982c/9456239/f83a06e7734a/jcm-11-04954-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/982c/9456239/a2d60c4fc4b5/jcm-11-04954-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/982c/9456239/d5f69770a125/jcm-11-04954-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/982c/9456239/dc82396fa6a8/jcm-11-04954-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/982c/9456239/f7d461d76055/jcm-11-04954-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/982c/9456239/38f7559d1be6/jcm-11-04954-g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/982c/9456239/a2d60c4fc4b5/jcm-11-04954-g006.jpg

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