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甲磺酸伊马替尼治疗的慢性髓性白血病患者不同反应组及分期中白细胞介素1β血清水平的评估

Assessment of interleukin 1β serum level in different responder groups and stages of chronic myeloid leukemia patients on imatinb mesylate therapy.

作者信息

Matti Bassam Francis, Saleem Maysoon Ali, Sabir Shahla'a Fadhil

机构信息

Baghdad Teaching Hospital, Clinical Hematology Department, Medical City, Baghdad, Iraq.

College of Medicine, Microbiology Department, Al-Mustansiriya University, Baghdad, Iraq.

出版信息

Indian J Hematol Blood Transfus. 2014 Dec;30(4):247-52. doi: 10.1007/s12288-014-0339-7. Epub 2014 Feb 7.

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the presence of an acquired mutation which affects the hematopoietic stem cell, leading to a striking overproduction of immature granulocytes. The first important clue to its pathogenesis the Philadelphia chromosome created by a reciprocal translocation between chromosomes 9 and 22 (t [9; 22] [q34; q11]). The development of the BCR-ABL-targeted imatinib mesylate represents a paradigm shift in the treatment of CML. Imatinib displays inhibitory activity against other kinase(s) that play a role in monocyte/macrophage development. Accordingly many studies revealed the role of cytokines in pathophysiology of myeloid neoplasia including participation of IL-1β in the pathogenesis of CML. This study designed to assess the behavior of IL-1β through newly diagnosed patients, different responders groups (optimal, suboptimal and failure cytogenetic response) and advanced stages (acceleration and crisis groups) of CML Iraqi patients whom receiving Imatinib mesylate (tyrosine kinase inhibitor), trying to elucidate the role of immunity in pathophysiology of CML disease development and treatments. In this study 96 Iraqi CML patients under imatinib mesylate treatment categorized by complete blood picture and fluorescent in situ hybridization analysis into different response groups and stages, then used an enzyme linked immunosorbent assay technique to assess serum level of IL-1β in each response group and advance stage (acceleration and transformed) of CML patients, in comparison to level in 32 healthy control subjects and 32 newly diagnosed CML. Out of 128 patients the mean serum of interleukin 1β level (pg/ml) for the newly diagnosed, optimal responded, suboptimal responded, failure cytogenetic and advance stage of CML were 6.53 ± 3.81, 18.47 ± 4.29, 18.69 ± 3.03, 5.73 ± 2.44, and 18.10 ± 3.10, respectively. While healthy was 12.17 ± 3.44. The measurement of IL-1β before and during treatment of CML patients may contribute to the early identification of responder and non responder patients, and help in the earlier choice and/or design of alternative therapeutic strategies.

摘要

慢性髓性白血病(CML)是一种骨髓增殖性疾病,其特征是存在一种影响造血干细胞的获得性突变,导致未成熟粒细胞显著过度增殖。其发病机制的首个重要线索是9号和22号染色体之间相互易位产生的费城染色体(t[9;22][q34;q11])。靶向BCR-ABL的甲磺酸伊马替尼的研发代表了CML治疗的范式转变。伊马替尼对在单核细胞/巨噬细胞发育中起作用的其他激酶具有抑制活性。因此,许多研究揭示了细胞因子在髓系肿瘤病理生理学中的作用,包括IL-1β参与CML的发病机制。本研究旨在通过新诊断的患者、不同反应组(最佳、次优和失败的细胞遗传学反应)以及接受甲磺酸伊马替尼(酪氨酸激酶抑制剂)治疗的伊拉克CML患者的晚期阶段(加速期和急变期)来评估IL-1β的表现,试图阐明免疫在CML疾病发展和治疗病理生理学中的作用。在本研究中,96例接受甲磺酸伊马替尼治疗的伊拉克CML患者通过全血细胞计数和荧光原位杂交分析被分类为不同的反应组和阶段,然后使用酶联免疫吸附测定技术评估每个反应组以及CML患者的晚期阶段(加速期和转化期)的血清IL-1β水平,并与32名健康对照受试者和32名新诊断的CML患者的水平进行比较。在128例患者中,新诊断的、反应最佳的、反应次优的、细胞遗传学失败的以及CML晚期阶段的白细胞介素1β平均血清水平(pg/ml)分别为6.53±3.81、18.47±4.29、18.69±3.03、5.73±2.44和18.10±3.10。而健康对照者为12.17±3.44。在CML患者治疗前和治疗期间测量IL-1β可能有助于早期识别反应者和无反应者,并有助于更早地选择和/或设计替代治疗策略。

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