慢性中性粒细胞白血病(CNL)是一种罕见的骨髓增殖性肿瘤(MPN)。由于其非特异性临床症状和缺乏特异性分子标志物,以前很难将其与中性粒细胞增加的其他疾病区分开来。然而,10年前CNL中CSF3R突变的发现以及2016年世界卫生组织(WHO)对诊断标准的更新,使CNL进入了分子诊断的新时代.下一代测序(NGS)技术已导致CNL中许多突变基因的鉴定。虽然CSF3R通常被认为是CNL的驱动突变,使用NGS在CNL中也检测到其他突变,包括其他信号通路基因的突变(CBL,JAK2NARS,PTPN11)和染色质修饰基因(ASXL1,SETBP1,EZH2),DNA甲基化基因(DNMT3A,TET2),骨髓相关转录因子基因(RUNX1,GATA2),和剪接和RNA代谢基因(SRSF2,U2AF1)。这些突变基因和CSF3R突变共存,以及克隆的不同进化序列,加深了CNL分子生物学的复杂性。这篇综述的目的是总结CNL在过去十年中的遗传研究发现,关注CNL中常见的突变基因及其临床意义,以及CNL中的克隆进化模式和突变获得序列,为CNL患者的合理管理提供依据。
Chronic neutrophilic leukemia (CNL) is a rare type of myeloproliferative neoplasm (MPN). Due to its nonspecific clinical symptoms and lack of specific molecular markers, it was previously difficult to distinguish it from other diseases with increased neutrophils. However, the discovery of the CSF3R mutation in CNL 10 years ago and the update of the diagnostic criteria by the World Health Organization (WHO) in 2016 brought CNL into a new era of molecular diagnosis. Next-generation sequencing (NGS) technology has led to the identification of numerous mutant genes in CNL. While CSF3R is commonly recognized as the driver mutation of CNL, other mutations have also been detected in CNL using NGS, including mutations in other signaling pathway genes (CBL, JAK2, NARS, PTPN11) and chromatin modification genes (ASXL1, SETBP1, EZH2), DNA methylation genes (DNMT3A, TET2), myeloid-related transcription factor genes (RUNX1, GATA2), and splicing and RNA metabolism genes (SRSF2, U2AF1). The coexistence of these mutated genes and CSF3R mutations, as well as the different evolutionary sequences of clones, deepens the complexity of CNL molecular biology. The purpose of this review is to summarize the genetic research findings of CNL in the last decade, focusing on the common mutated genes in CNL and their clinical significance, as well as the clonal evolution pattern and sequence of mutation acquisition in CNL, to provide a basis for the appropriate management of CNL patients.