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伊马替尼治疗的慢性髓性白血病患者骨髓切片中T细胞和B细胞增加以及BACH2表达模式改变

Increase of T and B cells and altered BACH2 expression patterns in bone marrow trephines of imatinib-treated patients with chronic myelogenous leukaemia.

作者信息

Von Laffert Maximilian, Hänel Mathias, Dietel Manfred, Anagnostopoulos Ioannis, Jöhrens Korinna

机构信息

Institute of Pathology, Charité Universitätsmedizin, D-10117 Berlin, Germany.

Department of Internal Medicine III, Klinikum Chemnitz gGmbH, D-09113 Chemnitz, Germany.

出版信息

Oncol Lett. 2016 Oct;12(4):2421-2428. doi: 10.3892/ol.2016.4964. Epub 2016 Aug 5.

Abstract

The effect of imatinib on T and B cells in patients with chronic myelogenous leukaemia (CML) is not well understood. An upregulation of the transcription factor Broad-complex-Tramtrack-Bric-a-Brac and Cap'n'collar 1 bZip transcription factor 2 (BACH2), which is involved in the development and differentiation of B cells, was demonstrated in a CML cell line treated with imatinib. The present study retrospectively analysed the expression and distribution of cluster of differentiation (CD)3, CD20 and BACH2 (per 1,000 cells), as well as the co-expression of CD20 and BACH2, using immunohistochemistry in serial bone marrow trephines obtained from 14 CML patients treated with imatinib in comparison to 17 patients with newly diagnosed CML and 6 control trephines. Bone marrow trephines of CML patients in remission under imatinib therapy exhibited significantly higher numbers of CD3 and CD20 infiltrates (partly ordered in aggregates) compared with patients with newly diagnosed CML and control individuals. Similarly, nuclear expression of BACH2 in granulopoietic cells was increased in CML patients treated with imatinib, which may represent the histological correlate of the positive treatment effect. Furthermore, since BACH2 is involved in B cell development, its altered expression patterns by imatinib may be one explanation for high B cell numbers, as revealed by CD20/BACH2 (nuclear)-positive cells. As the present data are preliminary, future prospective studies are required to assess the prognostic and predictive role of BACH2 in patients with CML under targeted therapy.

摘要

伊马替尼对慢性粒细胞白血病(CML)患者T细胞和B细胞的影响尚未完全明确。在接受伊马替尼治疗的CML细胞系中,已证实参与B细胞发育和分化的转录因子Broad-complex-Tramtrack-Bric-a-Brac和Cap'n'collar 1 bZip转录因子2(BACH2)上调。本研究采用免疫组织化学方法,回顾性分析了14例接受伊马替尼治疗的CML患者、17例新诊断CML患者以及6例对照骨髓环钻活检标本中分化簇(CD)3、CD20和BACH2(每千细胞)的表达和分布,以及CD20和BACH2的共表达情况。与新诊断的CML患者和对照个体相比,接受伊马替尼治疗处于缓解期的CML患者骨髓环钻活检标本中CD3和CD20浸润细胞数量显著增加(部分呈聚集排列)。同样,接受伊马替尼治疗的CML患者粒细胞中BACH2的核表达增加,这可能是治疗效果良好的组织学相关表现。此外,由于BACH2参与B细胞发育,伊马替尼对其表达模式的改变可能是CD20/BACH2(核)阳性细胞所显示的高B细胞数量的一种解释。鉴于目前的数据尚属初步,需要未来进行前瞻性研究,以评估BACH2在接受靶向治疗的CML患者中的预后和预测作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2390/5038374/7a8c6e510aab/ol-12-04-2421-g00.jpg

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