Department of Gastroenterology, Shimane University School of Medicine, 89-1, Enya-cho, Izumo, Shimane, 693-8501, Japan.
Division of Gastrointestinal Endoscopy, Shimane University Hospital, 89-1, Enya-cho, Izumo, Shimane, 693-8501, Japan.
BMC Gastroenterol. 2021 Jan 6;21(1):19. doi: 10.1186/s12876-020-01584-6.
Dasatinib is a second-generation tyrosine kinase inhibitor (TKI) developed for treatment of patients with chronic myeloid leukemia (CML). The drug has been shown to act as a potent multikinase inhibitor by blocking not only the BCR-ABL1 gene sequence but also the SRC kinase family, though unexpected adverse events such as pleural effusion have recently been reported in patients undergoing treatment with dasatinib. Hemorrhagic colitis is a unique gastrointestinal adverse events associated with dasatinib and its pathogenesis remains poorly understood.
We report here a case of dasatinib-induced asymptomatic colitis in a patient with CML, who showed no exacerbation in careful observations and maintained deep molecular response (DMR) during a 3-year period. In addition, we performed transcriptome analysis of inflamed colonic mucosa specimens to clarify the possible mechanism of colitis that develops in association with dasatinib administration. Our results demonstrated that differential gene expression, especially lymphocyte-associated genes and chemokines, is substantially involved in inflammation of colonic mucosa in affected patients.
Dasatinib induces immune-mediated colitis following lymphocyte infiltration.
达沙替尼是一种第二代酪氨酸激酶抑制剂（TKI），用于治疗慢性髓性白血病（CML）患者。该药物已被证明通过阻断不仅 BCR-ABL1 基因序列，而且 SRC 激酶家族，具有强大的多激酶抑制作用，尽管最近有报道称接受达沙替尼治疗的患者出现了意外的不良反应，如胸腔积液。出血性结肠炎是一种与达沙替尼相关的独特胃肠道不良反应，其发病机制尚不清楚。
我们在此报告一例 CML 患者的达沙替尼诱导的无症状性结肠炎，在 3 年期间，该患者在仔细观察下未出现病情恶化，并保持深度分子反应（DMR）。此外，我们对炎症性结肠黏膜标本进行了转录组分析，以阐明与达沙替尼给药相关的结肠炎的可能发病机制。我们的结果表明，差异基因表达，特别是淋巴细胞相关基因和趋化因子，与受影响患者的结肠黏膜炎症密切相关。
达沙替尼通过淋巴细胞浸润诱导免疫介导的结肠炎。
