5q31-33区域的染色体易位与一系列造血恶性肿瘤相关，其中一些涉及到血小板源性生长因子受体β（PDGFRB）基因。我们报告了一例急性髓细胞白血病（AML）患者，该患者携带NPM1基因（NPM1突变型AML）突变及亚克隆基因重排涉及PDGFRB基因。我们确定了一种新的融合基因STRN3::PDGFRB，是由t(5;14) (q32;q12)染色体重排所产生。顺序FISH结果证实，约15%的白血病细胞携带PDGFRB基因重排，表明STRN3::PDGFRB是亚克隆中一个之前未报道的融合基因。逆转录PCR（RT-PCR）和Sanger测序证实，这种融合基因由STRN3的外显子7与PDGFRB的外显子11融合而成，结果产生了一个包含Striatin-3的卷曲螺旋结构域以及PDGFRB的跨膜和胞内酪氨酸激酶结构域的嵌合蛋白质。这种新蛋白质有明显的胞质定位，并且具有致癌效应，如使Ba/F3细胞转化为生长因子非依赖性细胞并在小鼠中导致致命的骨髓增生异常综合征/髓细胞增生性肿瘤（MDS/MPN样病变）疾病，进而在二级移植体中转化为T细胞淋巴母细胞淋巴瘤。表达STRN3::PDGFRB或ETV6::PDGFRB的Ba/F3细胞对酪氨酸激酶抑制剂（TKIs）和selinexor敏感，但体外实验结果显示，伊马替尼和selinexor的联用有显著的协同效应，尽管只有单独使用伊马替尼可以延长T细胞突变接受者小鼠的生存时间。我们的发现表明了这种新的融合基因的致癌效应，并提供了AML克隆进化的见解，该进化过程受治疗选择的影响。此外，我们的结果为携带这种突变的患者提供了潜在的治疗选择，并强调了需谨慎选择治疗方法以防止不良副作用。© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.

Chromosome translocations in the 5q31-33 region are associated with a range of hematologic malignancies, some of which involve the platelet-derived growth factor receptor beta (PDGFRB) gene. We report a case of acute myeloid leukemia (AML) with a mutation in the NPM1 gene (NPM1-mut AML) and a subclonal gene rearrangement involving the PDGFRB gene. We identified a novel fusion gene, STRN3::PDGFRB, resulting from t(5;14) (q32;q12) chromosomal rearrangement. Sequential FISH confirmed that ~15% of leukemic cells carried the PDGFRB gene rearrangement, which suggests that STRN3::PDGFRB is a previously unreported fusion gene in a subclone. Reverse transcription PCR (RT-PCR) and Sanger sequencing confirmed that the fusion gene consisted of STRN3 exon 7 fused to PDGFRB exon 11, resulting in a chimeric protein containing the coiled-coil domain of striatin-3 and the transmembrane and intracellular tyrosine kinase domains of the PDGFRB. The new protein exhibited distinct cytoplasmic localization and had leukemogenic effects, as demonstrated by its ability to transform Ba/F3 cells to growth factor independence and cause a fatal myelodysplastic/myeloproliferative neoplasm (MDS/MPN)-like disease in mice, which then transformant to T-cell lymphoblastic lymphoma in secondary recipients. Ba/F3 cells expressing STRN3::PDGFRB or ETV6::PDGFRB were sensitive to tyrosine kinase inhibitors (TKIs) and selinexor, but in vitro experiments showed that the combination of imatinib and selinexor had a marked synergistic effect, although only the imatinib alone group could prolong the survival of T-cell blast transformation recipient mice. Our findings demonstrate the leukemogenic effects of the novel fusion gene and provide insights into the clone evolution of AML, which can be influenced by therapy selection. Furthermore, our results provide insight into the potential therapeutic options for patients with this type of mutation, as well as the need for careful consideration of treatment selection to prevent undesirable side effects.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.