Patnaik M M, Lasho T L, Vijayvargiya P, Finke C M, Hanson C A, Ketterling R P, Gangat N, Tefferi A
Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
Department of Laboratory Medicine, Mayo Clinic, Rochester, MN, USA.
Blood Cancer J. 2016 Jan 15;6(1):e385. doi: 10.1038/bcj.2015.113.
Mutations involving epigenetic regulators (TET260% and ASXL140%) 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.
涉及表观遗传调节因子（TET2约60%，ASXL1约40%）和剪接成分（SRSF2约50%）的突变在慢性粒单核细胞白血病（CMML）中很常见。在对175例CMML患者（66%为男性，中位年龄70岁）进行的27基因靶向捕获检测中，常见突变包括：TET2 46%，ASXL1 47%，SRSF2 45%和SETBP1 19%。共有172例（98%）患者至少有一个突变，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。在单因素分析中，ASXL1突变的存在（P=0.02）和TET2突变的缺失（P=0.03）对生存有不利影响；而同时存在的突变数量没有影响（P=0.3）。在包括血红蛋白、血小板计数、绝对单核细胞计数和循环未成熟髓系细胞的多因素分析（梅奥模型）中，ASXL1突变的存在（P=0.01）和TET2突变的缺失（P=0.003）保留了预后意义。患者被分为四类：ASXL1野生型/TET2野生型（n=56），ASXL1突变型/TET2野生型（n=31），ASXL1突变型/TET2突变型（n=50）和ASXL1野生型/TET2突变型（n=38）。生存数据显示，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突变型患者的生存情况有显著差异（38个月；P=0.016）（P=0.3）。我们证实了ASXL1突变带来的负面预后影响，并表明在没有ASXL1突变的情况下，TET2突变有有利影响。
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