Abstract：
We report a series of patients with CSF3R-mutant (CSF3Rmut) atypical chronic myeloid leukemia (aCML), chronic neutrophilic leukemia (CNL) or other hematologic malignancies. We included 25 patients: 5 aCML and 4 CNL CSF3Rmut patients; 1 aCML, 2 CNL, and 2 myelodysplastic/myeloproliferative neoplasm, not otherwise specified patients without CSF3R mutation; and 11 CSF3Rmut patients with other diseases [8 acute myeloid leukemia (AML), 1 chronic myelomonocytic leukemia (CMML), 1 myelodysplastic syndrome (MDS), and 1 acute lymphoblastic leukemia (ALL)]. Patients with aCML or CNL were tested by Sanger sequencing and pyrosequencing to identify CSF3R T618I. Twenty-two patients underwent gene panel analysis. CSF3R mutations, mostly T618I (8/9), were found at high frequencies in both aCML and CNL patients [5/6 aCML and 4/6 CNL]. Two aCML patients in early adulthood with CSF3R T618I and biallelic or homozygous CEBPA mutations without other mutations presented with increased blasts and exhibited remission for >6 years after transplantation. The other 7 CSF3Rmut aCML or CNL patients were elderly adults who all had ASXL1 mutations and frequently presented with SEBP1 and SRSF2 mutations. Five AML patients had CSF3R exon 14 or 15 point mutations, and 6 other patients (3 AML, 1 CMML, 1 MDS, and 1 ALL) had truncating mutations, demonstrating differences in leukocyte counts and mutation status. In conclusion, CSF3R mutations were found at a higher frequency in aCML patients than in previous studies, which might reflect ethnic differences. Additional studies are needed to confirm these findings and the relationship between CSF3R and CEBPA mutations.
摘要：
我们报告了一系列CSF3R突变（CSF3Rmut）非典型慢性粒细胞白血病（aCML）患者，慢性中性粒细胞白血病（CNL）或其他血液系统恶性肿瘤。我们纳入了25例患者：5例aCML和4例CNLCSF3Rmut患者；1例aCML，2CNL,和2骨髓增生异常/骨髓增殖性肿瘤，没有CSF3R突变的患者，以及11例CSF3Rmut患有其他疾病的患者[8例急性髓系白血病（AML），1慢性粒单核细胞白血病（CMML），1骨髓增生异常综合征（MDS），和1个急性淋巴细胞白血病（ALL）]。通过Sanger测序和焦磷酸测序对患有aCML或CNL的患者进行测试以鉴定CSF3RT618I。22例患者接受了基因面板分析。CSF3R突变,主要是T618I（8/9），在aCML和CNL患者中发现频率很高[5/6aCML和4/6CNL]。两名成年早期患有CSF3RT618I和双等位基因或纯合CEBPA突变而没有其他突变的aCML患者呈现母细胞增加，并在移植后>6年内表现出缓解。其他7例CSF3RmutaCML或CNL患者为均有ASXL1突变且频繁出现SEBP1和SRSF2突变的老年人。五名AML患者有CSF3R外显子14或15点突变，和其他6名患者(3名AML，1CMML,1MDS,和1ALL)具有截断突变，显示白细胞计数和突变状态的差异。总之,在aCML患者中发现CSF3R突变的频率高于以前的研究，这可能反映了种族差异。需要进一步的研究来证实这些发现以及CSF3R和CEBPA突变之间的关系。
