慢性中性粒细胞白血病(CNL)是一种罕见的骨髓增殖性肿瘤,其遗传特征是不存在费城染色体和BCR-ABL1融合基因,并且集落刺激因子3受体(CSF3R)的突变发生率很高。在CNL样品中已经认识到其他疾病修饰突变,描绘了一个独特的突变景观。尽管关于基因组畸变的知识基础越来越多,有代表性的CNL模型可以取得进一步的进展。为了解决这个差距,我们筛选了一大组可用的白血病细胞系,随后进行了详细的突变调查,重点是CNL相关的候选驱动基因。姐妹细胞系CNLBC-1和MOLM-20来自CNL患者,并带有CNL典型的分子标志,即几个基因的突变,例如CSF3R,ASXL1,EZH2,NRAS,SETBP1。使用这些经过验证和全面表征的模型将有助于了解CNL的病理生物学,并有助于告知治疗策略。
Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm that is genetically characterized by the absence of both the Philadelphia chromosome and BCR-ABL1 fusion gene and the high prevalence of mutations in the colony-stimulating factor 3 receptor (CSF3R). Additional disease-modifying mutations have been recognized in CNL samples, portraying a distinct mutational landscape. Despite the growing knowledge base on genomic aberrations, further progress could be gained from the availability of representative models of CNL. To address this gap, we screened a large panel of available leukemia cell lines, followed by a detailed mutational investigation with focus on the CNL-associated candidate driver genes. The sister cell lines CNLBC-1 and MOLM-20 were derived from a patient with CNL and carry CNL-typical molecular hallmarks, namely mutations in several genes, such as CSF3R, ASXL1, EZH2, NRAS, and SETBP1. The use of these validated and comprehensively characterized models will benefit the understanding of the pathobiology of CNL and help inform therapeutic strategies.