Table_1_Case Report: A novel FGFR1 fusion in acute B-lymphoblastic leukemia identified by RNA sequencing.docx

8p11 myeloproliferative syndrome is a rare hematological malignancy with aggressive course caused by the various translocation of FGFR1. In this study, a novel FGFR1 fusion was identified by RNA sequencing in a 28-year-old male patient with acute B-lymphoblastic leukemia. The patient harbors an in-frame fusion between KIF5B exon 15 and FGFR1 exon 10. The FGFR1 fusion and its protein expression was validated by Sanger sequencing and Western blot. Meanwhile, cytogenetic analysis reported a normal karyotype and targeted DNA sequencing identified no driver mutations, respectively. Despite he achieved complete remission after induction regimen, a relapse occurred and he became refractory to chemotherapy, and salvage haploidentical hematopoietic stem cell transplantation failed to control the progressive disease. In conclusion, we present the first case of KIF5B-FGFR1 fusion in hematological malignancy. These findings extend the spectrum of translocation in 8p11 myeloproliferative syndrome, and demonstrate the great prospect of RNA sequencing in clinical practice again.

8p11骨髓增殖综合征（8p11 myeloproliferative syndrome）是一类罕见的血液系统恶性肿瘤，病程呈侵袭性，由成纤维细胞生长因子受体1（fibroblast growth factor receptor 1, FGFR1）的多种易位诱发。本研究通过RNA测序（RNA sequencing），在1例28岁急性B淋巴细胞白血病（acute B-lymphoblastic leukemia）男性患者体内鉴定出一种新型FGFR1融合基因。该患者携带KIF5B第15号外显子与FGFR1第10号外显子之间的框内融合。研究人员通过桑格测序（Sanger sequencing）与蛋白质印迹（Western blot）验证了该FGFR1融合基因及其蛋白的表达。与此同时，细胞遗传学分析显示核型正常，靶向DNA测序（targeted DNA sequencing）未检出驱动突变。尽管患者经诱导化疗方案治疗后获得完全缓解，但随后出现复发，且对化疗产生耐药性，挽救性单倍体相合造血干细胞移植（haploidentical hematopoietic stem cell transplantation）未能控制病情的进展。综上，本研究首次报道了血液系统恶性肿瘤中存在KIF5B-FGFR1融合基因。上述发现拓展了8p11骨髓增殖综合征的易位谱，并再次证实了RNA测序在临床实践中的广阔应用前景。