Faculty of Life Sciences, Technical University of Braunschweig, 38106 Braunschweig, Germany.
Department of Human and Animal Cell Lines, Leibniz-Institute DSMZ-German Collection of Microorganisms and Cell Cultures, 38124 Braunschweig, Germany.
Curr Oncol. 2021 May 10;28(3):1790-1794. doi: 10.3390/curroncol28030166.
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.
慢性中性粒细胞白血病（CNL）是一种罕见的骨髓增殖性肿瘤，其遗传特征为既不存在费城染色体和 BCR-ABL1 融合基因，又普遍存在集落刺激因子 3 受体（CSF3R）突变。在 CNL 样本中还发现了其他疾病修饰突变，描绘了一个独特的突变景观。尽管对基因组异常的了解不断增加，但如果有代表性的 CNL 模型，可能会取得进一步的进展。为了解决这一差距，我们筛选了大量现有的白血病细胞系，然后对 CNL 相关候选驱动基因进行了详细的突变研究。姐妹细胞系 CNLBC-1 和 MOLM-20 源自一名患有 CNL 的患者，携带 CNL 典型的分子特征，即多个基因（如 CSF3R、ASXL1、EZH2、NRAS 和 SETBP1）发生突变。使用这些经过验证和全面表征的模型将有助于理解 CNL 的病理生物学，并有助于为治疗策略提供信息。
