VH4-34+ hairy cell leukemia, a new variant with poor prognosis despite standard therapy
VH4-34+ hairy cell leukemia, a new variant with poor prognosis despite standard therapy
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DOI：
10.1182/blood-2009-01-201731
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发表时间：
2009-11-19
期刊：
影响因子：
20.3
通讯作者：
Kreitman, Robert J.
中科院分区：
文献类型：
--
作者：
Arons, Evgeny;Suntum, Tara;Kreitman, Robert J.
毛细胞白血病变异型 (HCLv) 疾病负担高，缺乏 CD25 等典型抗原，并且对克拉屈滨等标准治疗反应不佳。有时，经典 HCL 患者反应不佳。尚未对 HCL 和 HCLv 的临床和分子特征进行比较。对表达免疫球蛋白 VH 链的重排进行了测序，其中包括来自 20 名 HCLv 患者的 22 个重排和来自 62 名经典 HCL 患者的 63 个重排。大多数患者正在寻求复发/难治性试验，代表预后不良的人群。 VH4-34 是一种常用于自身免疫性疾病的基因，在 8 名 (40%) HCLv 和 6 名 (10%) 经典 (P = .004) HCL 患者中观察到。与 71 个 VH4-34(-) 重排相比，14 个 VH4-34(+) 重排未突变的频率更高 (P < .001)，定义为与种系序列同源性超过 98%。 VH-434(+) 患者在诊断时具有较高的白细胞计数 (P = .002)、初始克拉屈滨后较低的缓解率 (P < .001) 和无进展生存期 (P = .007)，以及诊断后的总生存期较短 (P < .001)。与患者是否患有 HCLv 相比，缓解和生存与 VH4-34 状态的关系更为密切。 VH4-34(-) HCL 是一种重要的疾病，与之前描述的 HCLv 仅部分重叠。对初始单药克拉屈滨治疗的反应不佳；这些患者应考虑采用替代方法，包括抗体相关治疗。 （血。2009；114：4687-4695）
Hairy cell leukemia variant (HCLv) presents with high disease burden, lack of typical antigens like CD25, and poor response to standard treatments like cladribine. Occasionally, patients with classic HCL respond poorly. Clinical and molecular features of HCL and HCLv has not been compared. Rearrangements expressing immunoglobulin VH chain were sequenced, including 22 from 20 patients with HCLv and 63 from 62 patients with classic HCL. Most patients were seeking relapsed/refractory trials, representing a poor-prognosis population. VH4-34, a gene commonly used in autoimmune disorders, was observed in 8 (40%) HCLv and 6 (10%) classic (P = .004) HCL patients. Compared with 71 VH4-34(-) rearrangements, 14 VH4-34(+) rearrangements were more frequently (P < .001) unmutated, defined as greater than 98% homologous to germline sequence. VH-434(+) patients had greater white blood cell counts at diagnosis (P = .002), lower response rate ( P < .001) and progression-free survival ( P = .007) after initial cladribine, and shorter overall survival from diagnosis (P < .001). Response and survival were more closely related to VH4-34 status than to whether or not patients had HCLv. VH4-34(-) HCL is an important disorder that only partly overlaps with the previously described HCLv. Response to initial single-agent cladribine therapy is suboptimal; these patients should be considered for alternative approaches, including antibody-related therapy. ( Blood. 2009; 114:4687-4695)