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:Unmasking Cytomegalovirus Colitis: A Case of Haemorrhagic Colitis in a Patient with Chronic Myeloid Leukaemia on Dasatinib.
Unmasking Cytomegalovirus Colitis: A Case of Haemorrhagic Colitis in a Patient with Chronic Myeloid Leukaemia on Dasatinib.
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本病例强调了在接受 TKIs 治疗的 CML 患者中考虑 CMV 等机会性感染的重要性。鉴于 CMV 结肠炎与达沙替尼诱导的结肠炎在临床和内镜特征上存在重叠,组织病理学评估对于准确诊断和及时管理至关重要。学习要点:在接受达沙替尼治疗的免疫抑制患者中,出血性结肠炎可能掩盖潜在的感染。组织活检是及时诊断巨细胞病毒结肠炎的关键工具,使临床医生能够尽早开始治疗,从而预防不良结局。
酪氨酸激酶抑制剂(TKIs)是伴有BCR-ABL1易位的慢性髓性白血病(CML)的一线治疗药物。达沙替尼作为第二代TKI,与多种不良反应相关,如骨髓抑制、胸腔积液、腹泻和出血性结肠炎,发生率高达40%。此外,其对NK 细胞和T淋巴细胞的脱靶免疫调节作用可能导致潜伏感染的再激活,包括巨细胞病毒(CMV),后者是已知的结肠炎病因。病例报告:我们报告一例CMV相关性出血性结肠炎,患者为一名69岁女性,患有处于完全缓解期的CML,正在接受达沙替尼治疗。她因1个月的全身乏力、头晕和间歇性便血病史入院。就诊时,因出血性休克表现为低血压和心动过速。急诊结肠镜检查发现直肠、乙状结肠和横结肠有多发性小溃疡和糜烂,伴有活动性出血征象,予以止血夹处理。直肠活检最初显示轻度非特异性慢性炎症。因怀疑药物相关性结肠炎,达沙替尼被停用。然而,出院后免疫组化检查发现局限性CMV包涵体,促使患者再次入院并开始缬更昔洛韦治疗。
Tyrosine kinase inhibitors (TKIs) are the first-line treatment for chronic myeloid leukaemia (CML) with BCR-ABL1 translocation. Dasatinib, a second-generation TKI, is associated with a wide range of adverse effects such as myelosuppression, pleural effusion, diarrhoea, and haemorrhagic colitis in up to 40% of patients. Additionally, its off-target immunomodulatory effects on natural killer cells and T lymphocytes may lead to the reactivation of latent infections, including cytomegalovirus (CMV), a known cause of colitis. CASE REPORT: We present a case of CMV-associated haemorrhagic colitis in a 69-year-old woman with CML in complete remission, who was being treated with dasatinib. She was admitted to our hospital with a 1-month history of generalized weakness, light-headedness, and intermittent haematochezia. On presentation, she was hypotensive and tachycardic due to haemorrhagic shock. Urgent colonoscopy revealed multiple small ulcers and erosions in the rectum, sigmoid, and transverse colon with signs of active bleeding, which were managed with haemostatic clips. Rectal biopsy initially showed mild, non-specific chronic inflammation. Dasatinib was discontinued due to suspected drug-related colitis. However, post-discharge immunohistochemistry revealed localized CMV inclusions, prompting readmission and initiation of valganciclovir therapy.
This case highlights the importance of considering opportunistic infections such as CMV in CML patients receiving TKIs. Given the overlapping clinical and endoscopic features of CMV and dasatinib-induced colitis, histopathological evaluation is essential for accurate diagnosis and timely management. LEARNING POINTS: In immunosuppressed patients being treated with dasatinib, haemorrhagic colitis can mask an underlying infection.Tissue biopsy constitutes a key tool for promptly diagnosing cytomegalovirus colitis, enabling clinicians to start treatment early and thus prevent adverse outcomes.
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