母细胞性浆细胞样树突状细胞肿瘤发病机制、诊断和治疗的研究进展

Research progress in pathogenesis,diagnosis and treatment of blastic plasmacytoid dendritic cell neoplasm

母细胞性浆细胞样树突状细胞肿瘤(blastic plasmacytoid dendritic cell neoplasm,BPDCN)是一种罕见的血液学克隆性恶性肿瘤,来源于树突状细胞前体,常累及皮肤、骨髓及淋巴结,预后不佳。BPDCN的发病通常与复杂的核型、肿瘤抑制基因的频繁缺失以及影响DNA甲基化或染色质重塑途径的突变有关。目前,对BPDCN的治疗尚无统一标准,主要采用急性髓系白血病、急性淋巴母细胞白血病和淋巴瘤为主的方案,针对化疗有很高的反应,但中位无事件生存期通常很短,一般不到两年。异基因造血干细胞移植可改善BPDCN的预后,但复发率仍很高。2018年,SL-401被批准为首个针对2岁及以上BPDCN患者的靶向治疗。随着新的靶向治疗方法被引入,这些关于靶向表观遗传改变、特异性信号通路或肿瘤细胞表达抗原的新药显示出希望,并为运用靶向治疗的前瞻性研究铺平了道路。本文主要从BPDCN的发病机制、诊断和治疗方面进行综述,重点讨论新的靶向治疗。

Blastic plasmacytoid dendritic cell neoplasm(BPDCN)is a rare hematological clonal malignant tumor derived from a precursor of dendritic cells,often involving the skin,bone marrow and lymph nodes,with a poor prognosis.BPDCN is often associated with complex karyotypes,frequent deletions of tumor suppressor genes,and mutations affecting DNA methylation or chromatin remodeling pathways.At present,there is no unified standard for the treatment of BPDCN,and the regimen mainly adopts acute myeloid leukemia,acute lymphoblastic leukemia and lymphoma.It has a high response to chemotherapy,but the median eventless survival time is usually short,generally less than two years.Allogeneic hematopoietic stem cell transplantation can improve the prognosis of BPDCN,but the recurrence rate is still very high.In 2018,SL-401 was approved as the first targeted therapy for BPDCN patients 2 years and older.With the introduction of new targeted therapies,these data on new drugs that target epigenetic changes,specific signaling pathways or neoplasm cells expressing antigens show promise and pave the way for prospective studies using targeted therapies.In this paper,the pathogenesis,diagnosis and treatment of BPDCN are reviewed,and new targeted therapies are discussed.