Shanxi Medical University, Taiyuan, China.
Institute of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, China.
Int J Lab Hematol. 2022 Apr;44(2):364-370. doi: 10.1111/ijlh.13762. Epub 2021 Nov 24.
The colony-stimulating factor 3 receptor (CSF3R) controls the proliferation of myeloid progenitors and differentiation into neutrophils. However, the clinical features and prognostic significance of CSF3R mutations in primary acute myeloid leukemia (AML) patients are still unclear.
158 newly diagnosed AML patients were retrospectively evaluated in our study. Amplicon-based next-generation sequencing (NGS) and multiplex-nested reverse-transcription polymerase chain reaction (RT-PCR) were used to investigate the 34 genes and 43 fusion genes associated with leukemia. In addition, clinical features, mutation incidence, and survival outcomes were compared between patients with CSF3R mutation and patients with wild-type CSF3R.
In our study, CSF3R mutations were found in 7.6% (12/158) cases. The membrane-proximal amino acid substitution T618I (58.3%) was the most frequent mutation. CSF3R mutations were associated with higher WBC counts (P = .035). CEBPA mutation, TET2 mutation, and RUNX1-RUNX1T1 translocation were the most common co-mutations of CSF3R. The CSF3R gene was mutually exclusive with signal transduction genes (P = .029), while positively associated with TET2 mutations (P = .014). CSF3R mutations had no effect on CR1 (P = .935), R (P = .625) and OS (P = .1172). Patients with CSF3R mutations had a worse DFS (P = .0352) than those with wild-type CSF3R. Multivariate survival analysis showed that CSF3R mutation was an independent risk factor for DFS of primary AML patients (HR=2.048, 95%CI: 1.006-4.170, P = .048).
AML patients with CSF3R mutations had unique clinical features and gene co-mutation spectrum. CSF3R mutation was an independent risk factor for DFS and could be a potential prognostic marker and therapeutic target for Chinese primary AML patients.
集落刺激因子 3 受体（CSF3R）控制髓系祖细胞的增殖和向中性粒细胞的分化。然而，CSF3R 突变在原发性急性髓系白血病（AML）患者中的临床特征和预后意义仍不清楚。
本研究回顾性评估了 158 例新诊断的 AML 患者。采用基于扩增子的下一代测序（NGS）和多重巢式逆转录聚合酶链反应（RT-PCR）检测与白血病相关的 34 个基因和 43 个融合基因。此外，比较了 CSF3R 突变患者和 CSF3R 野生型患者的临床特征、突变发生率和生存结局。
在本研究中，发现 CSF3R 突变占 7.6%（12/158）。膜近端氨基酸取代 T618I（58.3%）是最常见的突变。CSF3R 突变与较高的白细胞计数相关（P=0.035）。CEBPA 突变、TET2 突变和 RUNX1-RUNX1T1 易位是 CSF3R 的最常见共突变。CSF3R 基因与信号转导基因相互排斥（P=0.029），而与 TET2 突变呈正相关（P=0.014）。CSF3R 突变对 CR1（P=0.935）、R（P=0.625）和 OS（P=0.1172）没有影响。CSF3R 突变患者的无病生存（DFS）较差（P=0.0352）。多变量生存分析显示，CSF3R 突变是原发性 AML 患者 DFS 的独立危险因素（HR=2.048，95%CI：1.006-4.170，P=0.048）。
AML 患者具有独特的临床特征和基因共突变谱。CSF3R 突变是 DFS 的独立危险因素，可能是中国原发性 AML 患者潜在的预后标志物和治疗靶点。
