PDF(Pubmed)
Abstract：
We previously reported the Marimo cell line, which was established from the bone marrow cells of a patient with essential thrombocythemia (ET) at the last stage after transformation to acute myeloid leukemia (AML). This cell line is widely used for the biological analysis of ET because it harbors CALR mutation. However, genetic processes during disease progression in the original patient were not analyzed. We sequentially analyzed the genetic status in the original patient samples during disease progression. The ET clone had already acquired CALR and MPL mutations, and TP53 and NRAS mutations affected the disease progression from ET to AML in this patient. Particularly, the variant allele frequency of the NRAS mutation increased along with the disease progression after transformation, and the NRAS-mutated clone selectively proliferated in vitro, resulting in the establishment of the Marimo cell line. Although CALR and MPL mutations co-existed, MPL was not expressed in Marimo cells or any clinical samples. Furthermore, mitogen-activated protein kinase (MAPK) but not the JAK2-STAT pathway was activated. These results collectively indicate that MAPK activation is mainly associated with the proliferation ability of Marimo cells.
摘要：
我们以前报道过Marimo细胞系,它是在转化为急性髓细胞性白血病（AML）后的最后阶段从原发性血小板增多症（ET）患者的骨髓细胞中建立的。该细胞系广泛用于ET的生物学分析，因为它具有CALR突变。然而,未分析原始患者疾病进展期间的遗传过程.我们依次分析了疾病进展过程中原始患者样本的遗传状态。ET克隆已经获得CALR和MPL突变，TP53和NRAS突变影响该患者从ET到AML的疾病进展。特别是,NRAS突变的变异等位基因频率随着转化后疾病进展而增加，NRAS突变的克隆在体外选择性增殖，导致Marimo细胞系的建立。虽然CALR和MPL突变共存，MPL在Marimo细胞或任何临床样品中不表达。此外，丝裂原活化蛋白激酶（MAPK）而不是JAK2-STAT途径被激活。这些结果共同表明MAPK活化主要与Marimo细胞的增殖能力有关。
