Zhang Qi-Guo, Wang Jing, Gong Wen-Yu, Jing Qi-Chuan
a Department of Hematology , The First People's Hospital of Chuzhou City , Chuzhou , People's Republic of China.
b Chuzhou Clinical College of Anhui Medical University , Chuzhou , People's Republic of China.
Hematology. 2019 Dec;24(1):455-458. doi: 10.1080/16078454.2019.1613291.
Objectives and importance: Chronic neutrophilic leukemia (CNL) is a distinct myeloproliferative neoplasm with a high prevalence (>80%) of mutations in the colony-stimulating factor 3 receptor (CSF3R); these mutations activate the receptor, leading to the proliferation of neutrophils that are a hallmark of CNL. Clinical presentation: We present a male patient who presented peripheral blood leukocytosis. On the basis of his morphological appearances and molecular findings he was determined to have a diagnosis of chronic neutrophilic leukemia. At a follow-up at 7 months, in addition to the CSF3R c.2373G > A (p.W791*) truncated mutation, another CSF3R mutation appeared as c.1853C > T(p.T618I). Discussion and conclusion: We present the first patient with a diagnosis of chronic neutrophilic leukemia with a c.2373G > A (p.W791*) truncated mutation of CSF3R. These findings elucidate a novel paradigm of CNL pathogenesis and explain how mutations drive the development of the disease. The order of acquisition of CSF3R mutations relative to mutations in epigenetic modifiers and the spliceosome have been determined only in isolated case reports; thus, further work is needed to understand the impact of mutation chronology on the clonal evolution and progression of CNL.
慢性嗜中性粒细胞白血病（CNL）是一种独特的骨髓增殖性肿瘤，集落刺激因子3受体（CSF3R）突变的发生率很高（>80%）；这些突变激活该受体，导致嗜中性粒细胞增殖，这是CNL的一个标志。临床表现：我们报告一名出现外周血白细胞增多的男性患者。根据其形态学表现和分子检测结果，他被诊断为慢性嗜中性粒细胞白血病。在7个月的随访中，除了CSF3R基因c.2373G＞A（p.W791*）截短突变外，另一个CSF3R突变c.1853C＞T（p.T618I）出现。讨论与结论：我们报告了首例诊断为慢性嗜中性粒细胞白血病且伴有CSF3R基因c.2373G＞A（p.W791*）截短突变的患者。这些发现阐明了CNL发病机制的新模式，并解释了突变如何驱动疾病的发展。相对于表观遗传修饰因子和剪接体突变而言，CSF3R突变获得的顺序仅在个别病例报告中有所确定；因此，需要进一步开展工作以了解突变时间顺序对CNL克隆进化和进展的影响。
