Arai Kosuke, Takagi Fumisato, Sonokawa Saeko, Suzuki Sayaka, Ito Eisaku, Takeuchi Kengo, Kumagai Takashi
Department of Hematology, Ome Municipal General Hospital.
Department of Pathology, Ome Municipal General Hospital.
Rinsho Ketsueki. 2018;59(1):51-57. doi: 10.11406/rinketsu.59.51.
A 69-year-old man visited a doctor because of systemic lymphadenopathy. Peripheral blood examination revealed leukocytosis, anemia, and decreased platelet count (WBC, 103,060/µl; lymph, 92.2%; Hb, 8.9 g/dl; and Plt, 4.1×10/µl). Bone marrow biopsy revealed that approximately 70% of nucleated cells were small, mature lymphoid cells with positive immunostaining for CD5, CD20, and CD23. He was diagnosed with chronic lymphocytic leukemia (CLL). The IgH/CCND1 translocation and ATM locus loss in 20% and 95% peripheral cells, respectively, were detected by fluorescence in situ hybridization. Immunostaining revealed that cyclin D1 was positive in approximately 30% bone marrow cells. As the positive rate of CCND1 fusion signal was low, the diagnosis of mantle cell lymphoma was excluded. In contrast, signals of ATM locus deletion were detected in most tumor cells. Therefore, we assessed that IgH/CCND1 translocations occurred during the natural clinical course of CLL with ATM locus deletion from the onset of disease. The secondary IgH/CCND1 translocation in CLL is rare, and all reported cases with such translocations received treatments with alkylating agents. This is the first report regarding secondary IgH/CCND1 translocation during the natural clinical course of CLL and may provide insights into CLL pathogenesis.
一名69岁男性因全身淋巴结肿大就诊。外周血检查显示白细胞增多、贫血和血小板计数降低（白细胞，103,060/µl；淋巴细胞，92.2%；血红蛋白，8.9 g/dl；血小板，4.1×10/µl）。骨髓活检显示，约70%的有核细胞为小的成熟淋巴细胞，CD5、CD20和CD23免疫染色呈阳性。他被诊断为慢性淋巴细胞白血病（CLL）。通过荧光原位杂交检测到20%的外周细胞中存在IgH/CCND1易位，95%的外周细胞中存在ATM基因座缺失。免疫染色显示，约30%的骨髓细胞中细胞周期蛋白D1呈阳性。由于CCND1融合信号的阳性率较低，排除了套细胞淋巴瘤的诊断。相反，在大多数肿瘤细胞中检测到了ATM基因座缺失信号。因此，我们评估IgH/CCND1易位发生在CLL自然临床病程中，且从疾病发作起就存在ATM基因座缺失。CLL中的继发性IgH/CCND1易位罕见，所有报道的此类易位病例均接受了烷化剂治疗。这是关于CLL自然临床病程中继发性IgH/CCND1易位的首次报道，可能为CLL发病机制提供见解。
