Identification of STRBP as a Novel JAK2 Fusion Partner Gene in a Young Adult With Philadelphia Chromosome-Like B-Lymphoblastic Leukemia.
Identification of STRBP as a Novel JAK2 Fusion Partner Gene in a Young Adult With Philadelphia Chromosome-Like B-Lymphoblastic Leukemia.
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在费城染色体样 B 淋巴细胞白血病年轻成人中鉴定 STRBP 作为新型 JAK2 融合伴侣基因
DOI：
10.3389/fonc.2020.611467
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发表时间：
2020
影响因子：
4.7
通讯作者：
Tang XW
中科院分区：
文献类型：
--
作者：
Zhang XY;Dai HP;Li Z;Yin J;Lang XP;Yang CX;Xiao S;Zhu MQ;Liu DD;Liu H;Shen HJ;Wu DP;Tang XW
费城染色体样B淋巴母细胞白血病（Ph样ALL）描述了一组遗传异质性、Ph阴性的实体，复发率高，预后差。在临床试验中研究了JAK抑制剂治疗反应的Ph样ALL患者中，约7%报告了Janus激酶2（JAK 2）重排。在这里，我们报告了一个新的STRBP-JAK 2融合基因在一个21岁的妇女与Ph样ALL。虽然观察到正常的核型，但在细胞遗传学上检测到迄今未报道的JAK 2重排。通过RNA测序鉴定STRBP-JAK 2融合体，并通过桑格测序验证。传统诱导化疗联合鲁索替尼治疗难治性Ph样ALL。患者同意输注抗CD 19和CD 22的自体嵌合抗原受体（CAR）T细胞，这诱导了形态学缓解。然后进行了单倍相合的干细胞移植;然而，她在移植后仅一个月就复发了。患者随后接受供体淋巴细胞输注，之后她实现并维持了微小残留疾病阴性缓解。然而，她在移植后7个月死于IV级移植物抗宿主病。总之，本报告描述了一种新的STRBP-JAK 2基因融合在一个非常积极的疾病过程中，Ph样ALL患者，这证明了耐化疗联合鲁索替尼，但对免疫治疗敏感。我们的研究表明，CAR-T细胞疗法可能是这种类型白血病的可行选择。
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.
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影响因子：
50.3
作者：
Roberts KG;Morin RD;Zhang J;Hirst M;Zhao Y;Su X;Chen SC;Payne-Turner D;Churchman ML;Harvey RC;Chen X;Kasap C;Yan C;Becksfort J;Finney RP;Teachey DT;Maude SL;Tse K;Moore R;Jones S;Mungall K;Birol I;Edmonson MN;Hu Y;Buetow KE;Chen IM;Carroll WL;Wei L;Ma J;Kleppe M;Levine RL;Garcia-Manero G;Larsen E;Shah NP;Devidas M;Reaman G;Smith M;Paugh SW;Evans WE;Grupp SA;Jeha S;Pui CH;Gerhard DS;Downing JR;Willman CL;Loh M;Hunger SP;Marra MA;Mullighan CG
通讯作者：
Mullighan CG
影响因子：
45.3
作者：
Roberts, Kathryn G.;Gu, Zhaohui;Mullighan, Charles G.
通讯作者：
Mullighan, Charles G.
影响因子：
7.5
作者：
Harvey, Richard C.;Tasian, Sarah K.
通讯作者：
Tasian, Sarah K.
DOI：
10.1016/j.clml.2011.02.007
发表时间：
2011-06
期刊：
Clinical lymphoma, myeloma & leukemia
影响因子：
--
作者：
Santos FP;Verstovsek S
通讯作者：
Verstovsek S
影响因子：
14.9
作者：
Coolidge, CJ;Patton, JG
通讯作者：
Patton, JG