Department of Dermatology, University of Rome Tor Vergata, Rome, Italy.
Clin Ther. 2009 Nov;31(11):2565-9. doi: 10.1016/j.clinthera.2009.11.018.
Chronic myeloid leukemia (CML) is a myeloproliferative disorder primarily characterized by the presence of the Philadelphia chromosome resulting from a reciprocal translocation between the long arms of chromosomes 9 and 22. This translocation determines a fusion gene, bcr-abl, which encodes a constitutively active protein, tyrosine kinase, resulting in decreased apoptosis, defective adhesion, and genomic instability in transformed cells. The tyrosine kinase activity and its effects represent a potential pharmacologic target of tyrosine kinase inhibitors, such as imatinib. Flare of Kaposi's sarcoma (KS) is well described in immunosuppressed patients treated with corticosteroids and rituximab, but has not yet been reported during treatment with imatinib.
We report a case of cutaneous KS lesions in a patient affected by CML treated with imatinib.
A 61-year-old white male patient (weight, 90 kg) was diagnosed with CML in March 2006 at the Division of Hematology, University of Rome "Tor Vergata," Rome, Italy. He was treated with imatinib 400 mg/d, which improved his general condition with few adverse effects. After 12 months of treatment, molecular biology showed an important reduction in the peripheral blood of the fusion oncoprotein bcr-abl p210-b3a2. However, at the same time, multiple cutaneous violaceous papular-nodular lesions appeared on his left forearm. A punch biopsy showed the presence of KS, whereas a polymerase chain reaction assay documented the presence of human herpes virus type 8 (HHV8) DNA in the skin lesion. Serologic HIV was negative and HHV8 viremia was under the limit of quantitation of the assay. Total body computed tomography scan did not reveal any mucosal or visceral lesion.
We present a case of a patient with CML who developed KS 12 months after starting treatment with imatinib 400 mg/d. The mechanism behind the development of the cutaneous lesions is unclear, and could have either a casual clinical association or be related to the study drug. According to the Naranjo adverse drug reaction probability scale, the development of KS in this case was probably associated with the imatinib treatment (score, 5-8).
慢性髓性白血病（CML）是一种骨髓增生性疾病，主要特征是存在费城染色体，这是由于 9 号和 22 号染色体长臂之间的相互易位导致的。该易位决定了融合基因 bcr-abl 的产生，该基因编码一种组成性激活的蛋白，酪氨酸激酶，导致转化细胞中的细胞凋亡减少、黏附功能缺陷和基因组不稳定。酪氨酸激酶的活性及其作用代表了酪氨酸激酶抑制剂（如伊马替尼）的潜在药理作用靶点。在接受皮质类固醇和利妥昔单抗治疗的免疫抑制患者中，卡波西肉瘤（KS）的爆发已有很好的描述，但在接受伊马替尼治疗时尚未报道。
我们报告了一例接受伊马替尼治疗的 CML 患者出现皮肤 KS 病变。
一名 61 岁白人男性（体重 90 公斤）于 2006 年 3 月在意大利罗马“Tor Vergata”大学血液学系诊断为 CML。他接受伊马替尼 400 mg/d 治疗，这改善了他的一般状况，仅有少数不良反应。治疗 12 个月后，分子生物学显示外周血融合癌蛋白 bcr-abl p210-b3a2 显著减少。然而，与此同时，他的左前臂出现了多个紫色丘疹性结节性皮损。皮肤活检显示存在 KS，聚合酶链反应检测显示皮肤病变中存在人类疱疹病毒 8 型（HHV8）DNA。血清 HIV 为阴性，HHV8 病毒血症低于检测限。全身计算机断层扫描未发现任何黏膜或内脏病变。
我们报告了一例 CML 患者在开始伊马替尼 400 mg/d 治疗 12 个月后出现 KS 的病例。皮肤病变发展的机制尚不清楚，可能与临床关联，也可能与研究药物有关。根据 Naranjo 药物不良反应概率量表，本例 KS 的发生可能与伊马替尼治疗有关（评分 5-8）。
