RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Hemophagocytic Lymphohistiocytosis Syndrome With Hepatic Involvement and Secondary to Acute B-cell Lymphocytic Leukemia: A Case Report.
Hemophagocytic Lymphohistiocytosis Syndrome With Hepatic Involvement and Secondary to Acute B-cell Lymphocytic Leukemia: A Case Report.
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噬血细胞性淋巴组织细胞增生症(HLH)是一种与巨噬细胞过度活化相关的过度活化综合征,巨噬细胞会产生大量肿瘤坏死因子-α和干扰素-γ。HLH常表现为T细胞和自然杀伤(NK)细胞调节功能减弱,这可由潜在的遗传原因、感染、自身免疫性疾病和/或继发于恶性肿瘤而发展而来。在此,我们描述了一例39岁男性,表现为主观发热和乏力。进一步检查发现高铁蛋白血症、高甘油三酯血症和NK细胞活性缺失,这强烈提示HLH。检查还发现转氨酶升高,提示肝脏受累,归因于HLH。骨髓活检显示细胞增多,而非HLH中通常见到的噬血现象。流式细胞术显示急性B淋巴细胞白血病,被确定为该患者HLH的病因。本病例突出了继发于B细胞恶性肿瘤的HLH的罕见表现。它强调了尽管使用广谱抗生素,对高热患者仍应保持高度临床怀疑的重要性。关于继发于恶性肿瘤的HLH的治疗,特别是相关信息有限,需要在该领域进一步研究以提高生存率。
Hemophagocytic lymphohistiocytosis (HLH) is a hyperactivation syndrome associated with the overactivation of macrophages, which produce enormous amounts of tumor necrosis factor-alpha and interferon-gamma. HLH often presents with diminished T-cell and natural killer (NK) cell regulation, which can develop due to underlying genetic causes, infections, autoimmune diseases, and/or secondary to malignancies.
Here, we describe the case of a 39-year-old man who presented with subjective fevers and fatigue.
Further workup revealed hyperferritinemia, hypertriglyceridemia, and absent NK-cell activity, which raised a strong suspicion for HLH. The workup also revealed elevated aminotransferases signaling hepatic involvement that was attributed to HLH. Bone marrow biopsy revealed hypercellularity instead of the hemophagocytosis usually seen in HLH. Flow cytometry revealed acute B-cell lymphocytic leukemia, which was identified as the cause of HLH in our patient.
This case highlights the rare presentation of HLH secondary to a B-cell malignancy. It addresses the importance of high clinical suspicion in patients with high fevers despite the use of broad-spectrum antibiotics. There is limited information on the treatment of HLH secondary to malignancies specifically, and further research in this area is needed to increase the survival rate.
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