Identification of STRBP as a Novel JAK2 Fusion Partner Gene in a Young Adult With Philadelphia Chromosome-Like B-Lymphoblastic Leukemia

被引:7
|
作者
Zhang, Xin-Yue [1 ,2 ]
Dai, Hai-Ping [1 ,2 ]
Li, Zheng [1 ,2 ]
Yin, Jia [1 ,2 ]
Lang, Xing-Ping [3 ]
Yang, Chun-Xiao [3 ]
Xiao, Sheng [4 ]
Zhu, Ming-Qing [1 ,2 ]
Liu, Dan-Dan [1 ,2 ]
Liu, Hong [1 ,2 ]
Shen, Hong-Jie [1 ,2 ]
Wu, De-Pei [1 ,2 ]
Tang, Xiao-Wen [1 ,2 ]
机构
[1] Soochow Univ, Natl Clin Res Ctr Hematol Dis, Jiangsu Inst Hematol, Affiliated Hosp 1, Suzhou, Peoples R China
[2] Soochow Univ, Inst Blood & Marrow Transplantat, Collaborat Innovat Ctr Hematol, Suzhou, Peoples R China
[3] Sano Suzhou Precis Med Co Ltd, Suzhou, Peoples R China
[4] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA
来源
FRONTIERS IN ONCOLOGY | 2021年 / 10卷
基金
国家重点研发计划; 中国国家自然科学基金;
关键词
fusion gene; STRBP-JAK2; Ph-like; chimeric antigen receptor; B-lymphoblastic leukemia; BINDING PROTEIN; KINASE; STRATEGIES;
D O I
10.3389/fonc.2020.611467
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Philadelphia chromosome-like B-lymphoblastic leukemia (Ph-like ALL) describes a group of genetically heterogeneous, Ph-negative entities with high relapse rates and poor prognoses. A Janus-kinase-2 (JAK2) rearrangement has been reported in approximately 7% of Ph-like ALL patients whose therapeutic responses to JAK inhibitors have been studied in clinical trials. Here, we report a novel STRBP-JAK2 fusion gene in a 21-year-old woman with Ph-like ALL. Although a normal karyotype was observed, a hitherto unreported JAK2 rearrangement was detected cytogenetically. STRBP-JAK2 fusion was identified by RNA sequencing and validated by Sanger sequencing. The Ph-like ALL proved refractory to traditional induction chemotherapy combined with ruxolitinib. The patient consented to infusion of autologous chimeric antigen receptor (CAR) T cells against both CD19 and CD22, which induced morphologic remission. Haplo-identical stem cell transplantation was then performed; however, she suffered relapse at just one month after transplantation. The patient subsequently received donor lymphocyte infusion after which she achieved and maintained a minimal residual disease negative remission. However, she succumbed to grade IV graft-versus-host disease 7 months post-transplant. In conclusion, this report describes a novel STRBP-JAK2 gene fusion in a Ph-like ALL patient with a very aggressive disease course, which proved resistant to chemotherapy combined with ruxolitinib but sensitive to immunotherapy. Our study suggests that CAR T-cell therapy may be a viable option for this type of leukemia.
引用
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页数:6
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