Department of Hematology and Oncology, University Medical Centre Mannheim, Mannheim, Germany.
MLL Munich Leukemia Laboratory, Munich, Germany.
Leukemia. 2016 Jan;30(1):136-43. doi: 10.1038/leu.2015.284. Epub 2015 Oct 14.
Most patients with KIT D816V(+) advanced systemic mastocytosis (SM) are characterized by somatic mutations in additional genes. We sought to clarify the prognostic impact of such mutations. Genotype and clinical characteristics of 70 multi-mutated KIT D816V(+) advanced SM patients were included in univariate and multivariate analyses. The most frequently identified mutated genes were TET2 (n=33 of 70 patients), SRSF2 (n=30), ASXL1 (n=20), RUNX1 (n=16) and JAK2 (n=11). In univariate analysis, overall survival (OS) was adversely influenced by mutations in SRSF2 (P<0.0001), ASXL1 (P=0.002) and RUNX1 (P=0.03), but was not influenced by mutations in TET2 or JAK2. In multivariate analysis, SRSF2 and ASXL1 remained the most predictive adverse indicators concerning OS. Furthermore, we found that inferior OS and adverse clinical characteristics were significantly influenced by the number of mutated genes in the SRSF2/ASXL1/RUNX1 (S/A/R) panel (P<0.0001). In conclusion, the presence and number of mutated genes within the S/A/R panel are adversely associated with advanced disease and poor survival in KIT D816V(+) SM. On the basis of these findings, inclusion of molecular markers should be considered in upcoming prognostic scoring systems for patients with SM.
大多数 KIT D816V(+) 晚期系统性肥大细胞增多症 (SM) 患者存在其他基因的体细胞突变。我们旨在阐明这些突变的预后影响。在单变量和多变量分析中纳入了 70 例多突变 KIT D816V(+) 晚期 SM 患者的基因型和临床特征。最常鉴定到的突变基因是 TET2（n=33/70 例）、SRSF2（n=30）、ASXL1（n=20）、RUNX1（n=16）和 JAK2（n=11）。在单变量分析中，SRSF2（P<0.0001）、ASXL1（P=0.002）和 RUNX1（P=0.03）的突变对总体生存（OS）有不利影响，但 TET2 或 JAK2 的突变没有影响。在多变量分析中，SRSF2 和 ASXL1 仍然是 OS 最具预测性的不良指标。此外，我们发现 SRSF2/ASXL1/RUNX1（S/A/R）面板中的突变基因数量对 OS 和不良临床特征有显著影响（P<0.0001）。总之，S/A/R 面板中存在和突变基因的数量与 KIT D816V(+) SM 中的晚期疾病和不良生存相关。基于这些发现，在即将到来的 SM 患者预后评分系统中应考虑纳入分子标志物。
