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目的探讨TLS-ERG融合基因对于儿童急性白血病的影响。方法回顾及总结分析2006年1月-2014年12月在北京儿童医院血液肿瘤中心诊断急性白血病且TLS-ERG融合基因阳性患儿的临床特征、治疗、危险度评估及预后。结果 1500例急性白血病患儿中检测出10例(0.6%)伴有TLS-ERG融合基因,其中男7例,女3例,中位年龄8岁,急性淋巴细胞白血病(ALL)6例,急性髓细胞白血病(AML)4例。6例ALL患儿中,免疫分型:4例为普通B淋巴细胞表型,1例为前B淋巴细胞表型,1例为带髓系标记的B淋巴细胞表型;危险度评估:2例为标危,4例为中危。4例AML患儿中,3例为AML-M2型,1例为AML-M5型。ALL患儿按照中国儿童白血病协作组(CCLG)-ALL 2008方案进行化疗,6例均在诱导缓解期达到完全缓解,按照化疗方案规律治疗,定期检测微小残留病(MRD)均小于1×10~(-4)。4例AML患儿中,2例患儿在第一疗程ADE(阿糖胞苷+柔红霉素十依托泊苷)化疗第21d复查骨穿提示未缓解,放弃治疗;1例患儿完成第一轮ADE化疗后骨髓完全缓解,按照化疗方案完成两轮ADE、MIT+ARA(米托蒽醌+阿糖胞苷)、CLASP(阿糖胞苷+左旋门冬酰胺酶)化疗后复发,后放弃治疗;1例患儿第一疗程化疗后完全缓解,后经过2疗程ADE、MIT/ARA、CLASP后骨髓细胞学完全缓解,TS-ERG融合基因仍阳性,故行父亲6/10HLA半相合造血干细胞移植,随访至今。结论 TLS-ERG融合基因在儿童急性白血病中阳性率低,但在ALL及AML患儿中均可发生。根据本中心资料,该融合基因对于ALL患儿的治疗及预后影响不大,但伴有TLS-ERG融合基因的急性髓细胞白血病患儿治疗困难,预后较差。该融合基因发生率较低,单中心资料有限,故需要多中心更大宗的资料进一步证实。
Objective To investigate the effect of TLS-ERG fusion gene on childhood acute leukemia. Methods The clinical features, treatment, risk assessment and prognosis of children with acute leukemia and positive TLS-ERG fusion gene were analyzed retrospectively and summarized from January 2006 to December 2014 in Children’s Hospital of Beijing. Results TLS-ERG fusion gene was detected in 10 cases (0.6%) of 1500 children with acute leukemia, including 7 males and 3 females, with a median age of 8 years, acute lymphoblastic leukemia (ALL) in 6 cases, acute Myeloid leukemia (AML) in 4 cases. In 6 children with ALL, the immunophenotypes were as follows: 4 cases were normal B lymphocyte phenotype, 1 case was pre-B lymphocyte phenotype and 1 case was myeloid lineage B lymphocyte phenotype. Risk assessment: 2 Cases of standard risk, 4 cases were in danger. Of the 4 children with AML, 3 were AML-M2 and 1 was AML-M5. ALL children under the China Children’s Leukemia Cooperative Group (CCLG) -ALL 2008 regimen chemotherapy, 6 patients were in the induction of remission to achieve complete remission, according to the regular chemotherapy regimen, regular detection of minimal residual disease (MRD) were less than 1 × 10 ~ (-4). In 4 children with AML, 2 children underwent the first course of ADE (cytarabine + daunorubicin and etoposide) chemotherapy for 21 days, After a round of ADE chemotherapy bone marrow completely relieved, according to the chemotherapy program to complete two rounds of ADE, MIT + ARA (mitoxantrone + cytarabine), CLASP (cytarabine + L-asparaginase) recurrence after chemotherapy, after Give up treatment; 1 case of complete remission after chemotherapy in the first course of treatment, after 2 courses of ADE, MIT / ARA, CLASP bone marrow cytology complete remission, TS-ERG fusion gene is still positive, so his father 6 / 10HLA semi- Stem cell transplantation, up to now. Conclusion The positive rate of TLS-ERG fusion gene in childhood acute leukemia is low, but it can occur in ALL and AML children. According to our data, the fusion gene has little effect on the treatment and prognosis of children with ALL. However, children with acute myeloid leukemia with TLS-ERG fusion gene have poor prognosis. The low incidence of fusion gene, single-center data is limited, so need a larger number of centers to further confirm the information.