Department of Hemato-Oncology, Faculty of Medicine and Dentistry, Palacký University Olomouc and University Hospital Olomouc, Olomouc, Czech Republic.
Int J Lab Hematol. 2021 Oct;43(5):1070-1077. doi: 10.1111/ijlh.13504. Epub 2021 Mar 18.
Driver mutations in Philadelphia chromosome-negative myeloproliferative neoplasms are well known. In the past, whole-genome sequencing identified nondriver mutations in other genes, potentially contributing to evolution of malignant clones.
Next-generation sequencing was used to assess the presence of any mutations in 14 candidate genes at the point of diagnosis and the resultant impact on the clinical course of the disease.
The study analysed 63 patients with myelofibrosis (MF). Nondriver mutations were detected in 44% of them. The most frequently affected genes were ASXL1 (27%), TET2 (11%) and SF3B1 (6%). The frequency of such mutations was highest in primary MF (59%) and lowest in the prefibrotic phase of primary MF (21%). Patients with prognostically unfavourable sequence variants in genes had significantly worse overall survival (53 vs 71 months; HR = 2.77; 95% CI 1.17-6.56; P = .017).
In our study, multivariate analysis proved DIPSS to be the only significant factor to predict patient survival. DIPSS contains all of the important clinical and laboratory factors except genetic changes. Stratification of patients according to DIPSS is still beneficial although there are newer and improved scoring systems like GIPSS or MIPSS70. Assessing subclonal mutations in candidate genes during diagnosis may aid in the identification of high-risk MF patients and is therefore relevant for making a prediction for overall survival more accurate.
费城染色体阴性骨髓增殖性肿瘤中的驱动基因突变众所周知。过去，全基因组测序鉴定出其他基因中的非驱动突变，这些突变可能有助于恶性克隆的进化。
采用下一代测序技术在诊断时评估 14 个候选基因中任何突变的存在情况及其对疾病临床过程的影响。
本研究分析了 63 例骨髓纤维化（MF）患者。其中 44%检测到非驱动突变。受影响最频繁的基因是 ASXL1（27%）、TET2（11%）和 SF3B1（6%）。这些突变在原发性 MF 中发生率最高（59%），在原发性 MF 的纤维化前期发生率最低（21%）。在基因中具有预后不良序列变异的患者总生存显著较差（53 个月与 71 个月；HR=2.77；95%CI 1.17-6.56；P=0.017）。
在我们的研究中，多变量分析证明 DIPSS 是唯一能够预测患者生存的重要因素。DIPSS 包含所有重要的临床和实验室因素，除了遗传变化。尽管有更新、更完善的评分系统，如 GIPSS 或 MIPSS70，根据 DIPSS 对患者进行分层仍然是有益的。在诊断时评估候选基因中的亚克隆突变可能有助于识别高风险 MF 患者，因此对于更准确地预测总生存具有重要意义。
