文章：

ASXL1和TET2突变在慢性粒单核细胞白血病中的预后交互作用

Prognostic interaction between ASXL1 and TET2 mutations in chronic myelomonocytic leukemia

原文发布日期：2016-01-15

DOI: 10.1038/bcj.2015.113

类型: Original Article

开放获取: 是

英文摘要：

Mutations involving epigenetic regulators (TET2~60% and ASXL1~40%) and splicing components (SRSF2~50%) are frequent in chronic myelomonocytic leukemia (CMML). On a 27-gene targeted capture panel performed on 175 CMML patients (66% males, median age 70 years), common mutations included: TET2 46%, ASXL1 47%, SRSF2 45% and SETBP1 19%. A total of 172 (98%) patients had at least one mutation, 21 (12%) had 2, 24 (14%) had 3 and 30 (17%) had >3 mutations. In a univariate analysis, the presence of ASXL1 mutations (P=0.02) and the absence of TET2 mutations (P=0.03), adversely impacted survival; while the number of concurrent mutations had no impact (P=0.3). In a multivariable analysis that included hemoglobin, platelet count, absolute monocyte count and circulating immature myeloid cells (Mayo model), the presence of ASXL1 mutations (P=0.01) and absence of TET2 mutations (P=0.003) retained prognostic significance. Patients were stratified into four categories: ASXL1wt/TET2wt (n=56), ASXL1mut/TET2wt (n=31), ASXL1mut/TET2mut (n=50) and ASXL1wt/TET2mut (n=38). Survival data demonstrated a significant difference in favor of ASXL1wt/TET2mut (38 months; P=0.016), compared with those with ASXL1wt/TET2wt (19 months), ASXL1mut/TET2wt (21 months) and ASXL1mut/TET2mut (16 months) (P=0.3). We confirm the negative prognostic impact imparted by ASXL1 mutations and suggest a favorable impact from TET2 mutations in the absence of ASXL1 mutations.

摘要翻译： 

慢性粒单核细胞白血病（CMML）中常见表观遗传调控因子（TET2约60%、ASXL1约40%）和剪接组件（SRSF2约50%）的突变。通过对175例CMML患者（66%男性，中位年龄70岁）进行27基因靶向捕获测序 panel 分析，发现常见突变包括：TET2 46%、ASXL1 47%、SRSF2 45% 和 SETBP1 19%。总计172例（98%）患者至少存在一个突变，21例（12%）有2个突变，24例（14%）有3个突变，30例（17%）有超过3个突变。单因素分析显示，ASXL1突变（P=0.02）和TET2突变缺失（P=0.03）对生存期产生不利影响，而共存突变数量无显著影响（P=0.3）。在多因素分析（包含血红蛋白、血小板计数、绝对单核细胞计数及循环幼稚髓系细胞等梅奥模型参数）中，ASXL1突变（P=0.01）和TET2突变缺失（P=0.003）仍保持预后意义。将患者分为四组：ASXL1野生型/TET2野生型（56例）、ASXL1突变型/TET2野生型（31例）、ASXL1突变型/TET2突变型（50例）及ASXL1野生型/TET2突变型（38例）。生存数据表明，与ASXL1野生型/TET2野生型（19个月）、ASXL1突变型/TET2野生型（21个月）和ASXL1突变型/TET2突变型（16个月）相比，ASXL1野生型/TET2突变型患者中位生存期显著延长（38个月；P=0.016），而其他三组间无显著差异（P=0.3）。本研究证实ASXL1突变具有负面预后影响，并提示在无ASXL1突变时，TET2突变可能产生有利影响。

原文链接：

Prognostic interaction between ASXL1 and TET2 mutations in chronic myelomonocytic leukemia