张坤龙;王宁玲;徐修才;杨林海;储金华;汪燕;涂松济;

• 1:安徽医科大学第二附属医院儿科

摘要(Abstract)：

目的研究急性淋巴细胞白血病(ALL)患儿染色体畸变所致融合基因与临床危险度分层及治疗的关系。方法采用多重RT-PCR方法检测儿童ALL的常见融合基因,结合染色体核型分析、免疫表型及临床资料对152例ALL患儿进行临床研究。结果 152例ALL患儿中有43例(29.5%)具有9种常见融合基因表达,包括TEL/AML1、BCR/ABL(P190)、BCR/ABL(P210)、E2A/PBX1、MLL/ENL、MLL/AF9、TLS/ERG、CBF/MYH11、Hox11。TEL/AML1融合基因阳性23例,其中1例放弃治疗,1例因早期治疗反应不良,评估为高危,其他21例均早期治疗反应良好,目前停药10例(停药时间4~30个月),11例仍为完全缓解(CR),1例停药18个月后骨髓复发。E2A/PBX1融合基因阳性4例,其中3例评估为中危,目前均CR中,1例因早期治疗反应不良,评估为高危,化疗过程中复发死亡;BCR/ABL(P190)阳性5例,BCR/ABL(P210)阳性3例,其中5例行骨髓移植治疗(4例移植后数月骨髓复发,1例CR中),1例选择高危方案化疗后骨髓复发,另外2例临床未缓解,放弃治疗;MLL基因阳性2例,均评估为中危,1例MLL/AF9,经强化疗后目前已停药18个月,1例MLL/ENL,在化疗过程中复发,放弃治疗;TLS/ERG融合基因1例,早期治疗反应不良,经强化疗后达CR,目前已停药20个月;Hox11融合基因阳性4例,均评估为中危,化疗后3例CR中,1例因复发放弃治疗。结论 TEL/AML1表达者化疗效果良好;BCR/ABL、MLL基因重排等化疗效果差,需骨髓移植或强烈化疗。采用多重RT-PCR方法可快速同时检测儿童急性白血病29种常见融合基因,完善白血病的MICM分型、指导临床个体化治疗。

关键词(KeyWords)： 儿童;急性淋巴细胞白血病;融合基因;多重RT-PCR;临床研究

Abstract:

Keywords:

基金项目(Foundation): 安徽省人口和计划生育科研课题2010(25)

作者(Author): 张坤龙;王宁玲;徐修才;杨林海;储金华;汪燕;涂松济;

Email:

DOI:

参考文献(References)：

• 1 .Vardiman JW,Harris NL,Brunning RD.The World Health Organization(WHO)classification of the myeloid neoplasms.Blood,2002,100:2292-2302.
• 2 .中华医学会儿科学分会血液学组,中华儿科杂志编辑委员会.儿童急性淋巴细胞白血病诊疗建议(第三次修订草案).中华儿科杂志,2006,44:392-395.
• 3 .儿童急性淋巴细胞白血病诊疗研究协作组.上海儿童医学中心急性淋巴细胞白血病2005方案疗效多中心研究.中华儿科杂志,2013,51:495-501.
• 4 .Pallisgaard N,Horland P,Riishoj DC,et al.Multiplex reverse transcription-polyymerase chain reaction for simultaneous screening of 29 translocations and chromosomal aberrations in acute leukemia.Blood,1998,92:574-588.
• 5 .Szczepanski T,Harrison CJ,van Dongen JJ.Genetic aberrations in paediatric acute leukaemias and implications for management of patients.Lancet Oncol,2010,11:880-889.
• 6 .Chen B,Wang YY,Shen Y,et al.Newly diagnosed acute lymphoblastie leukemia in China(I):Abnormal genetic patterns in1346 childhood and adult cases and their comparison with the reports from Western countries.Leukemia,2012,26:1608-1616.
• 7 .Pui CH,Carroll WL,Meshinchi S,et al.Biology,Risk Stratification,and Therapy of Pediatric Acute Leukemias:An Update.J Clin Oncol,2011,29:551-565.
• 8 .Schultz KR,Bowman WP,Aledo A,et al.Improved early eventfree survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia:A Children's Oncology Group study.J Clin Oncol,2009,27:5175-5181.
• 9 .Meyer C,Marsehalek R.LDI-PCR:identification of known and unknown gone fusions of the human MLL gene.Methods Mol Biol,2009,538:71-83.
• 10 .Balgobind BV,Raimondi SC,Harbott J,et al.Novel prognostic subgroups in childhood 1lq23/MLL-rearranged acute myeloid leukemia:results of an international retrospective study.Blood,2009,114:2489-2496.
• 11 .Eid MA,Attia M,Abdou S,et al.BAALC and ERG expression in acute myeloid leukemia with normal karyotype:impact on prognosis.Int J Lab Hematol,2010,32:197-205.
• 12 .胡彩莲,柴忆欢.HOX11原癌基因的活化对儿童急性白血病预后的影响.肿瘤,2007,12:1006-1007.
• 13 .Pakakasama S,Kajanachumpol S,Kanjanaponqkul S,et al.Simple multiplex RT-PCR for identifying common fusion transcripts in childhood acute leukemia.Int J LabHematol,2008,30:286-291.