Ewing’s sarcoma is an enigmatic malignancy of progenitor cell origin, driven by transcription factor oncogenic fusions. About 85% of ESFT cases harbor the t(11;22) translocation and express the fusion protein EWS-FLI...Ewing’s sarcoma is an enigmatic malignancy of progenitor cell origin, driven by transcription factor oncogenic fusions. About 85% of ESFT cases harbor the t(11;22) translocation and express the fusion protein EWS-FLI. Both bone marrow-derived human Mesenchymal stem cells and Neural crest stem cells are permissive for EWS-FLI1 expression that initiates transition to ESFT-like cellular phenotype. Diagnosis of Ewing’s tumor is based on pathologic and molecular findings. The hypoxia enhances the malignancy of ESFT invasive capacity. An ALDHhigh subpopulation of Ewing’s sarcoma cells, capable of self-renewal, tumor initiation and resistant to chemotherapy in vitro, are not resistant to YK-4-279. Intensive high-dose chemotherapy followed by stem-cell reconstitution was used for ESFT patients in second remission. Plerixafor in combination with G-CSF is an effective enhance stem cell mobilization regimen for stem cell collection with lowest success rate in patients with neuroblastoma. The ESFT-derived antigens EZH2(666) and CHM1(319) are suitable targets for protective allo-restricted human CD8(+) T-cell responses against non-immunogenic ESFT. Primitive neuroectodermal features and MSC origin are both compatible with G(D2) aberrant expression and explore G(D2) immune targeting in ESFT.展开更多
许多骨与软组织肿瘤中存在染色体易位的现象,其中对尤文肉瘤家族肿瘤(Ewing sarcoma family of tumors,ESFT)中染色体易位的研究最早且最为深入。约85%左右的ESFT患者存在t(11;22)(q24;q12)染色体易位,由其编码的融合蛋白EWS/FLI1是导致...许多骨与软组织肿瘤中存在染色体易位的现象,其中对尤文肉瘤家族肿瘤(Ewing sarcoma family of tumors,ESFT)中染色体易位的研究最早且最为深入。约85%左右的ESFT患者存在t(11;22)(q24;q12)染色体易位,由其编码的融合蛋白EWS/FLI1是导致ESFT发生和发展的关键因素。因此,对EWS/FLI1进一步研究可以为ESFT的诊断、治疗和预后等提供新的靶点。本文结合近几年的最新报道,对EWS/FLI1在ESFT发生和发展中的作用机制以及靶向治疗等方面的最新进展做一综述。展开更多
文摘Ewing’s sarcoma is an enigmatic malignancy of progenitor cell origin, driven by transcription factor oncogenic fusions. About 85% of ESFT cases harbor the t(11;22) translocation and express the fusion protein EWS-FLI. Both bone marrow-derived human Mesenchymal stem cells and Neural crest stem cells are permissive for EWS-FLI1 expression that initiates transition to ESFT-like cellular phenotype. Diagnosis of Ewing’s tumor is based on pathologic and molecular findings. The hypoxia enhances the malignancy of ESFT invasive capacity. An ALDHhigh subpopulation of Ewing’s sarcoma cells, capable of self-renewal, tumor initiation and resistant to chemotherapy in vitro, are not resistant to YK-4-279. Intensive high-dose chemotherapy followed by stem-cell reconstitution was used for ESFT patients in second remission. Plerixafor in combination with G-CSF is an effective enhance stem cell mobilization regimen for stem cell collection with lowest success rate in patients with neuroblastoma. The ESFT-derived antigens EZH2(666) and CHM1(319) are suitable targets for protective allo-restricted human CD8(+) T-cell responses against non-immunogenic ESFT. Primitive neuroectodermal features and MSC origin are both compatible with G(D2) aberrant expression and explore G(D2) immune targeting in ESFT.
文摘许多骨与软组织肿瘤中存在染色体易位的现象,其中对尤文肉瘤家族肿瘤(Ewing sarcoma family of tumors,ESFT)中染色体易位的研究最早且最为深入。约85%左右的ESFT患者存在t(11;22)(q24;q12)染色体易位,由其编码的融合蛋白EWS/FLI1是导致ESFT发生和发展的关键因素。因此,对EWS/FLI1进一步研究可以为ESFT的诊断、治疗和预后等提供新的靶点。本文结合近几年的最新报道,对EWS/FLI1在ESFT发生和发展中的作用机制以及靶向治疗等方面的最新进展做一综述。
