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巨核细胞中 GATA-1、IL-6 和 IL-8 的表达差异与伴有病态造血的浆细胞肿瘤患者血小板计数的维持有关。

Difference in megakaryocyte expression of GATA-1, IL-6, and IL-8 associated with maintenance of platelet counts in patients with plasma cell neoplasm with dysmegakaryopoiesis.

机构信息

Department of Laboratory Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea.

Department of Laboratory Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Republic of Korea.

出版信息

Exp Hematol. 2019 May;73:13-17.e2. doi: 10.1016/j.exphem.2019.02.005. Epub 2019 Feb 27.

Abstract

Dysmegakaryopoiesis is a diagnostic criterion for myelodysplastic syndrome (MDS), which accompanies thrombocytopenia. Recently, dysmegakaryopoiesis was reported in patients with plasma cell neoplasm (PCN). Although these patients maintained normal platelet counts, disease progressed, with most bone marrow cells being replaced by plasma cells. Several studies reported that dysmegakaryopoiesis was induced by inflammatory mechanisms; however, the exact mechanism underlying dysmegakaryopoiesis remains unknown. This study aimed to investigate whether changes in the megakaryocytic expression of GATA-1, pro-inflammatory cytokines (interleukin [IL]-6 and IL-8), and CD9 affect platelet counts and dysmegakaryopoiesis in patients with PCN and MDS. A total 114 patients were examined and categorized into four groups: MDS with dysmegakaryopoiesis (34 patients), PCN without dysmegakaryopoiesis (36 patients), PCN with dysmegakaryopoiesis (19 patients), and lymphoma without bone marrow infiltration (25 patients). Expression of GATA-1, IL-6, IL-8, and CD9 in megakaryocytes was assessed by immunohistochemical (IHC) staining of paraffin-embedded bone marrow sections. Localized expression of transcription factor and cytokines was observed in megakaryocytes. Furthermore, expression of GATA-1, IL-6, and IL-8 significantly differed (all p values < 0.05). Decreased GATA-1 expression was identified in MDS. Decreased IL-6 expression was observed in PCN and MDS. Moreover, decreased IL-8 expression was associated with dysmegakaryopoiesis, regardless of whether platelet counts were maintained. In conclusion, PCN patients with dysmegakaryopoiesis had normal platelet counts, and their megakaryocytes showed decreased IL-6 and IL-8 expression and normal GATA-1 expression. The differences in the megakaryocytic expression of cytokines in PCN and MDS with dysmegakaryopoiesis may be applicable to future therapeutic strategies.

摘要

巨核细胞发育不良是骨髓增生异常综合征(MDS)的诊断标准之一,常伴有血小板减少症。最近,浆细胞肿瘤(PCN)患者也出现了巨核细胞发育不良。尽管这些患者的血小板计数正常,但疾病仍在进展,大多数骨髓细胞被浆细胞取代。有几项研究报道,巨核细胞发育不良是由炎症机制引起的;然而,巨核细胞发育不良的确切机制尚不清楚。本研究旨在探讨 PCN 和 MDS 患者巨核细胞中 GATA-1、促炎细胞因子(白细胞介素 [IL]-6 和 IL-8)和 CD9 的表达变化是否会影响血小板计数和巨核细胞发育不良。共检查了 114 例患者,并分为四组:MDS 伴巨核细胞发育不良(34 例)、PCN 不伴巨核细胞发育不良(36 例)、PCN 伴巨核细胞发育不良(19 例)和淋巴瘤无骨髓浸润(25 例)。通过石蜡包埋骨 髓切片的免疫组织化学(IHC)染色评估巨核细胞中 GATA-1、IL-6、IL-8 和 CD9 的表达。观察到转录因子和细胞因子在巨核细胞中的局灶性表达。此外,GATA-1、IL-6 和 IL-8 的表达差异显著(均 p 值<0.05)。MDS 中 GATA-1 表达降低。PCN 和 MDS 中 IL-6 表达降低。此外,IL-8 表达降低与巨核细胞发育不良有关,与血小板计数是否维持无关。总之,伴巨核细胞发育不良的 PCN 患者血小板计数正常,其巨核细胞表现出 IL-6 和 IL-8 表达降低和 GATA-1 表达正常。PCN 和 MDS 伴巨核细胞发育不良患者巨核细胞中细胞因子表达的差异可能适用于未来的治疗策略。

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