Abstract：
CSF3R activating mutation is a genetic hallmark of chronic neutrophilic leukemia (CNL), and is also present in a subset of atypical chronic myeloid leukemia (aCML), but infrequent in other myeloid neoplasms. However, the occurrence of CSF3R mutations in various myeloid neoplasms is not well studied. Here we evaluate the spectrum of CSF3R mutations and the clinicopathologic features of CSF3R mutated myeloid neoplasms. We retrospectively identified CSF3R mutations in a variety of myeloid neoplasms: two CNL, three atypical chronic myeloid leukemia (aCML), nine acute myeloid leukemia (AML), one chronic myelomonocytic leukemia, and one myeloproliferative neoplasm. The prototypic T618I mutation was found in 50% of cases: CNL (2/2), aCML (2/3) and AML (4/9). We observed a new recurrent CSF3R mutation Q776* in 25% of cases, and a potential-germline mutation in a 20-year-old patient. Co-occurring mutations were often in epigenetic modifier and spliceosome. IDH/RUNX1 and tumor suppressor mutations were frequent in AML but absent in CNL/aCML. All CNL/aCML patients succumbed within 2-years of diagnosis. We demonstrate that CSF3R mutations are not restricted to CNL. CNL and aCML show similar clinicopathologic and molecular features, suggesting that CNL may be best classified as myelodysplastic/myeloproliferative neoplasm rather than myeloproliferative neoplasm.
摘要：
CSF3R激活突变是慢性中性粒细胞白血病（CNL）的遗传标志，并且也存在于非典型慢性粒细胞白血病（aCML）的一个子集中，但在其他髓系肿瘤中很少见。然而,CSF3R突变在各种髓系肿瘤中的发生尚未得到很好的研究.在这里，我们评估CSF3R突变谱和CSF3R突变髓系肿瘤的临床病理特征。我们回顾性地鉴定了多种髓系肿瘤中的CSF3R突变：两种CNL，三种非典型慢性粒细胞白血病（aCML），九急性髓系白血病（AML），一个慢性粒单核细胞白血病，和一个骨髓增殖性肿瘤。在50％的病例中发现了原型T618I突变：CNL（2/2），ACML(2/3)和AML(4/9)。我们在25%的病例中观察到新的复发CSF3R突变Q776*，以及一名20岁患者的潜在种系突变。共同发生的突变通常发生在表观遗传修饰体和剪接体中。IDH/RUNX1和肿瘤抑制突变在AML中常见，但在CNL/aCML中不存在。所有CNL/aCML患者在诊断后2年内死亡。我们证明CSF3R突变不限于CNL。CNL和aCML显示相似的临床病理和分子特征，这表明CNL最好被归类为骨髓增生异常/骨髓增殖性肿瘤，而不是骨髓增殖性肿瘤。
