The Royal Marsden Hospital and the Institute of Cancer Research, Sutton, UK.
Curr Oncol Rep. 2020 Apr 16;22(5):42. doi: 10.1007/s11912-020-00911-0.
To summarise diagnostic clinical/laboratory findings and highlight differences between classical hairy cell leukaemia (HCLc) and hairy cell leukaemia variant (HCLv). Discussion of prognosis and current treatment indications including novel therapies, linked to understanding of the underlying molecular pathogenesis.
Improved understanding of the underlying pathogenesis of HCLc, particularly the causative mutation BRAF V600E, leading to constitutive activation of the MEK/ERK signalling pathway and increased cell proliferation. HCLc is caused by BRAF V600E mutation in most cases. Purine nucleoside analogue (PNA) therapy is the mainstay of treatment, with the addition of rituximab, improving response and minimal residual disease (MRD) clearance. Despite excellent responses to PNAs, many patients will eventually relapse, requiring further therapy. Rarely, patients are refractory to PNA therapy. In relapsed/refractory patients, novel targeted therapies include BRAF inhibitors (BRAFi), anti-CD22 immunoconjugate moxetumomab and Bruton tyrosine kinase inhibitors (BTKi). HCLv has a worse prognosis with median overall survival (OS), only 7-9 years, despite the combination of PNA/rituximab improving front-line response. Moxetumomab or ibrutinib may be a viable treatment but lacks substantial evidence.
总结经典毛细胞白血病（HCLc）和毛细胞白血病变异型（HCLv）的诊断临床/实验室发现，并突出两者之间的差异。讨论预后和当前的治疗指征，包括与理解潜在分子发病机制相关的新型治疗方法。
对 HCLc 的潜在发病机制有了更好的理解，特别是导致 MEK/ERK 信号通路持续激活和细胞增殖增加的致病突变 BRAF V600E。在大多数情况下，HCLc 是由 BRAF V600E 突变引起的。嘌呤核苷类似物（PNA）治疗是主要的治疗方法，联合利妥昔单抗可提高反应率和微小残留病灶（MRD）清除率。尽管对 PNA 有极好的反应，但许多患者最终仍会复发，需要进一步治疗。极少数患者对 PNA 治疗有耐药性。在复发/难治性患者中，新型靶向治疗包括 BRAF 抑制剂（BRAFi）、抗 CD22 免疫偶联物莫替莫单抗和布鲁顿酪氨酸激酶抑制剂（BTKi）。尽管 PNA/利妥昔单抗联合治疗可改善一线反应，但 HCLv 的预后较差，总生存期（OS）中位数仅为 7-9 年。莫替莫umab 或伊布替尼可能是一种可行的治疗方法，但缺乏大量证据。
