TEL/AML1、BCR/ABL、E2A/PBX1、MLL/AF4阳性儿童急性淋巴细胞白血病的临床特点及预后

目的探讨儿童急性淋巴细胞白血病（ALL）TEL/AML1、BCR/ABL、E2A/PBX1、MLL/AF4四种融合基因的表达及其临床诊治意义。方法用实时荧光定量PCR(RQ-PCR)方法检测TEL/AML1、BCR/ABL（p190和p210两种亚型）、E2A/PBX1、MLL/AF4四种融合基因在312例ALL患儿中的表达情况，并总结融合基因阳性患儿的临床和生物学特点、治疗反应及预后情况。结果（1）融合基因阳性共120例，TEL/AML1阳性组72例(23.1%)，BCR/ABL阳性组22例(7.1%)，p190 16例（5.1%）、p210 6例（1.9%），E2A/PBX1阳性组18例(5.8%)，MLL/AF4阳性组8例(2.6%)。（2）TEL/AML1阳性组诊断时WBC平均值为(18.02±6.45)×109/L，诱导化疗结束完全缓解率(CR)100%，随访期间无复发；BCR/ABL阳性组发病时年龄(9.40±3.55)岁，诱导化疗结束CR 81.8%，强化治疗末仍有6例融合基因未转阴，随访中有8例（36.3%）复发，8例死亡；E2A/PBX1阳性组全部按高危标准给予化疗，诱导化疗结束CR 88.9%，强化治疗期末仍有3例基因微量表达，随访中2例复发；MLL/AF4阳性组发病时WBC(38.41±9.30)×109/L，强化治疗期末仍有2例基因呈阳性，随访中均复发死亡。结论融合基因可作为ALL危险度分层、监测微小残留病、判断预后的重要指标之一。

Clinical Features and Prognosis in Childhood Acute Plymphoblastic Leukemia with TEL/AML1,BCR/ABL,E2A/PBX1 and MLL/AF4 Positive

Objective To explore the expression and clinical significance of TEL/AML1,BCR/ABL,E2A/PBX1 and MLL/AF4 fusion gene in childhood acute lymphoblastic leukemia(ALL).Methods Bone marrow samples were collected from 312 children with newly diagnosed ALL,and E2A/PBX1,BCR/ABLp190(e1a2)and p210(b2a3,b3a2) isoforms,TEL/AML1 and MLL/AF4 fusion gene were detected by RQ-PCR.Meanwhile,Clinico-biological characteristic,therapeutic response and outcome were retrospectively analyzed.Results(1) The fusion genes were positive in 120 ALL children.72 cases(23.1%) expressed TEL/AML1,22 cases(7.1%) expressed BCR-ABL(including 16 cases(5.1%)p190 and 6 cases(1.9%) p210,18 cases(5.8%) expressed E2A/PBX1 and 8 cases(2.6%) expressed MLL/AF4).(2) In TEL/AML1 positive children,the leukocyte count was(18.02±6.45)×109/L with a 100% complete remission(CR) rate and none relapsed during follow-up.In BCR/ABL positive children,the mean age was(9.40±3.55) years old with 81.8% CR rate.6 cases still expressed the fusion gene at the end of intensive treatment.8 children relapsed and 8 children died during follow-up.In E2A/PBX1 positive children,all of them were given chemotherapy according to high risk standard.The CR rate was 88.9%.Three cases expressed micro-content fusion gene at the end of intensive treatment.2 cases relapsed during follow-up.In MLL/AF4 positive children,the leukocyte count was(41.53±9.46)×109/L.2 cases still expressed the fusion gene at the end of intensive treatment,and both of them relapsed and died.Conclusion Fusion genes are important indexes for risk stratification,MRD monitoring and prognosis estimation in children with ALL.