Ishii Shoko, Arakawa Yasuhiro, Ishii Hiroto, Yokoyama Kazuaki, Yokoyama Hiroki, Saito Takeshi, Yano Shingo
Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Department of Clinical Pharmacology and Therapeutics, The Jikei University School of Medicine, Tokyo, Japan.
Int J Hematol. 2025 Jun;121(6):782-791. doi: 10.1007/s12185-025-03944-y. Epub 2025 Feb 20.
Mixed phenotype acute leukemia (MPAL) is a rare and aggressive form of leukemia with a poor prognosis and no established treatment. In this study, we established a novel leukemic cell line, JMPAL-1, from a specimen of a 69-year-old patient with Philadelphia chromosome-positive MPAL. Flow cytometry showed that JMPAL-1 expresses B-cell markers but not myeloperoxidase. A genomic analysis of JMPAL-1 cells revealed the BCR::ABL1 fusion gene, missense mutation in PAX5, homozygous deletion of CDKN2A/CDKN2B, and BRAF amplification. This cell line was stroma-dependent in proliferation and required co-culturing with mouse bone marrow-derived mesenchymal cells (9-15C). Knowing the differences between JMPAL-1 and patient leukemia cells may improve understanding of the in vivo versus in vitro behavior of leukemia, clonal selection, and transformation. The stroma-dependent growth pattern of JMPAL-1 also provides a unique platform to study tumor-stromal interactions and their role in leukemic cell survival and drug resistance. Our study highlights the importance of establishing preclinical models such as JMPAL-1 and performing detailed cytogenetic analysis to develop targeted therapies in line with the pathogenesis of the disease.
混合表型急性白血病（MPAL）是一种罕见且侵袭性强的白血病，预后较差且尚无既定治疗方法。在本研究中，我们从一名69岁费城染色体阳性MPAL患者的标本中建立了一种新型白血病细胞系JMPAL-1。流式细胞术显示JMPAL-1表达B细胞标志物，但不表达髓过氧化物酶。对JMPAL-1细胞的基因组分析揭示了BCR::ABL1融合基因、PAX5中的错义突变、CDKN2A/CDKN2B的纯合缺失以及BRAF扩增。该细胞系在增殖方面依赖基质，需要与小鼠骨髓来源的间充质细胞（9-15C）共培养。了解JMPAL-1与患者白血病细胞之间的差异可能有助于增进对白血病体内与体外行为、克隆选择和转化的理解。JMPAL-1的基质依赖性生长模式也为研究肿瘤-基质相互作用及其在白血病细胞存活和耐药性中的作用提供了一个独特的平台。我们的研究强调了建立如JMPAL-1这样的临床前模型并进行详细细胞遗传学分析以根据疾病发病机制开发靶向治疗方法的重要性。
