Rapid Molecular Response to Dasatinib in a Pediatric Relapsed Acute Lymphoblastic Leukemia With NCOR1-LYN Fusion
Rapid Molecular Response to Dasatinib in a Pediatric Relapsed Acute Lymphoblastic Leukemia With NCOR1-LYN Fusion
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达沙替尼对 NCOR1-LYN 融合儿童复发性急性淋巴细胞白血病的快速分子反应
DOI：
10.3389/fonc.2020.00359
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发表时间：
2020-03-20
影响因子：
4.7
通讯作者：
Tang, Xiao-Wen
中科院分区：
文献类型：
--
作者：
Dai, Hai-Ping;Yin, Jia;Tang, Xiao-Wen
背景：费城染色体样急性淋巴细胞白血病（Ph 样 ALL）与高治疗失败率和不良预后相关。与 10% 的 Ph 样 ALL 类似，ABL/Src 家族激酶被激活，可以通过酪氨酸激酶抑制剂进行治疗。 LYN 是 ABL/Src-酪氨酸激酶家族的成员。迄今为止，在 5 例造血系统恶性肿瘤中发现体细胞 LYN 重排，但均未接受酪氨酸激酶抑制剂治疗。 病例介绍：一名患有复发性 B-ALL 的 6 岁男孩对再诱导化疗没有反应。随后，他接受了 ABL1 酪氨酸激酶抑制剂达沙替尼治疗，并在 2 周内实现了完全缓解。随后进行单倍体同种异体干细胞移植（allo-HSCT），并在移植后 8 周开始达沙替尼维持治疗。 allo-HSCT后10个月，他的微小残留病阴性缓解。结果：他的骨髓核型显示8号和17号染色体之间平衡易位，导致测序证实的NCOR1-LYN融合基因。结论：虽然许多AML和B-ALL患者中描述了LYN过度表达，但基因内LYN重排是罕见的事件。我们首次提出证据表明达沙替尼可有效治疗 NCOR-LYN 融合的儿童 B-ALL。
Background: Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is associated with high rates of treatment failure and poor outcome. Activation of ABL/Src family kinases is found in similar to 10% of Ph-like ALL, which can be therapeutically targeted by tyrosine kinase inhibitors. LYN is a member of the ABL/Src-tyrosine kinase family. Somatic LYN rearrangements are found in 5 cases of hematopoietic malignancies so far, although none of them were treated with tyrosine kinase inhibitors.Case presentation: A 6-year-old boy with relapsed B-ALL had no response to reinduction chemotherapy. He was then treated with the ABL1 tyrosine kinase inhibitor dasatinib and achieved complete remission within 2 weeks. Haploidentical allogenic stem cell transplantation (allo-HSCT) was subsequently performed and maintenance therapy with dasatinib initiated 8 weeks post-transplantation. He has been in minimal residual disease negative remission for 10 months after allo-HSCT.Result: His bone marrow karyotype showed a balanced translocation between chromosomes 8 and 17, leading to a NCOR1-LYN fusion gene confirmed with sequencing.Conclusion: Although LYN overexpression is described in many AML and B-ALL patients, intragenic LYN rearrangement is a rare event. For the first time, we present evidence that dasatinib is effective in treating a pediatric B-ALL with NCOR-LYN fusion.