Section of Hematology, Department of Medicine, University of Verona, Verona, Italy.
Renal Unit, Department of Medicine, University Hospital of Verona, Verona, Italy.
Exp Hematol Oncol. 2013 Aug 8;2:22. doi: 10.1186/2162-3619-2-22. eCollection 2013.
We report here on the diagnosis and successful treatment of a case of hairy cell leukemia (HCL) that arose 15 years after kidney transplantation in a 51-year-old patient. As soon as the diagnosis was made, HCL was treated with 2-CDA, obtaining complete hematological remission. Immunosuppression with the calcineurin inhibitor cyclosporin was maintained, and the graft was preserved. In kidney transplant recipients supported with immunosuppressive drugs, post-transplant lymphoproliferative diseases (PTLDs) are frequent and typically related to immunosuppression via a loss of control of infectious/EBV-related proliferative stimuli. To date, HCL has not been considered among PTLDs. Recently, however, the oncogenic mutation V600E of the BRAF protein kinase has been found to be a hallmark of HCL, and calcineurin inhibitors have been shown to interfere with signaling downstream of V600E BRAF early on by counteracting senescence-associated mechanisms that protect against the oncogenic potential of the mutated kinase. Such a biochemical link between the oncogene-dependent signaling and calcineurin inhibitor activities suggests that HCL in transplanted patients might be a peculiar type of PTLD based on the presence of a specific mutation. This mechanism might also be involved in other neoplasias bearing the same or similar mutations, such as melanoma and non-melanoma skin cancer.
我们在此报告一例 51 岁患者在肾移植后 15 年发生的毛细胞白血病(HCL)的诊断和成功治疗。诊断后,立即采用 2-CDA 治疗 HCL,获得完全血液学缓解。维持使用钙调神经磷酸酶抑制剂环孢素进行免疫抑制,同时保留移植物。在接受免疫抑制药物支持的肾移植受者中,移植后淋巴增殖性疾病(PTLD)很常见,通常与通过控制感染/EBV 相关增殖刺激物的丧失导致的免疫抑制有关。迄今为止,HCL 尚未被认为是 PTLD 之一。然而,最近发现 BRAF 蛋白激酶的致癌突变 V600E 是 HCL 的标志,钙调神经磷酸酶抑制剂通过抵消衰老相关机制,早期干扰 V600E BRAF 的信号转导,从而保护突变激酶的致癌潜能。这种癌基因依赖性信号和钙调神经磷酸酶抑制剂活性之间的生化联系表明,移植患者中的 HCL 可能是一种基于特定突变的特殊类型的 PTLD。这种机制也可能涉及其他具有相同或相似突变的肿瘤,如黑色素瘤和非黑色素瘤皮肤癌。