急性白血病相关基因检测的临床意义-现代医学

急性白血病相关基因检测的临床意义

单位：1. 南京医科大学附属淮安第一医院检验科, 江苏淮安 223300;
2. 南京医科大学附属淮安第一医院血液科, 江苏淮安 223300

分类号：R733.71

出版年·卷·期（页码）：2017·36·第十一期（1594-1597）

摘要：

目的：探讨急性白血病（acute luekemia，AL）相关融合基因与基因突变在临床诊断、指导治疗、判断预后中的意义。方法：采用多重巢式RT-PCR与基因测序技术检测65例AL患者相关融合基因及基因突变，同时结合患者免疫分型、染色体核型及治疗经过，分析患者的预后生存。结果：65例AL中15例急性淋巴细胞白血病（23.1%），50例急性髓系白血病（76.9%）。融合基因阳性率为50.8%，基因突变率为27.7%。其中5例患者BCR-ABL1融合基因阳性（7.7%），6例PML/RARA融合基因阳性（9.2%），11例FLT3-ITD基因突变（16.9%），7例AML1-ETO融合基因阳性（10.8%），7例EVI1融合基因阳性（10.8%），7例NPM1突变（10.8%），3例CEBPA基因突变（4.6%），3例C-kit/D 816V基因突变（4.6%），4例HOX11融合基因阳性（6.2%），10例患者合并两种以上融合基因或突变。65例AL患者3年总生存期（OS）生存率为20%，3年无疾病进展生存期（PFS）为18%。融合基因或突变阳性患者3年OS与融合基因或突变阴性患者3年OS（P=0.052）、PFS（P=0.269）差异无统计学意义。单纯AML1-ETO或CEBPA双突变AL预后较好，缓解率高，长期生存率高。伴PML/RARA的7例患者，无论是否合并FLT3-ITD等基因突变，均达完全缓解，且3年内无复发。结论：多重PCR及基因测序技术能够快速检测AL相关基因，在AL的诊断、预后及疗效判断中起重要作用，并能进一步监测微小残留病，指导临床个体化治疗。

Objective:To investigate the significance of fusion gene and gene mutation in acute leukemia clinical diagnosis, guided therapy and prognosis. Methods:Using multiple nested RT-PCR and gene sequencing analysis, related fusion gene and gene mutation were detected in 65 acute leukemia patients, and combining with the patients' immunophenotype, chromosome karyotype and treatment procedure, the prognosis and survival of patients were analyzed. Results:65 cases of AL patients, including 15 cases of acute lymphocytic leukemia (23.1%) and 50 cases of acute myeloid leukemia (76.9%), the positive fusion gene rate was 50.8%, gene mutation rate was 27.7%, including 5 cases with positive BCR-ABL1 fusion gene (7.7%), 6 cases with positive PML/RARA fusion gene (9.2%), 11 cases with FLT3-ITD gene mutation (16.9%), 7 cases with positive AML1-ETO fusion gene (10.8%), 7 cases with positive EVI1 fusion gene (10.8%), 7 cases with NPM1 gene mutation (10.8%), 3 cases with CEBPA gene mutation (4.6%), 3 cases with C-kit/D 816V gene mutation (4.6%), 4 cases with positive HOX11 fusion gene (6.2%), 10 cases with two or more of the above fusion genes or mutations. The 3-year overall survival (OS) rate of 65 cases of patients was 20%, and progression-free survival (PFS) rate was 18%. Three years of OS (P=0.052) and PFS (P=0.269) were not statistically significant in the patients with positive/negative fusion gene or mutant. Patients only with AML1-ETO or CEBPA double mutation had a better survival rate, a higher remission rate and better long-term survival rates. 7 cases of patients were PML/RARA positive, with or without FLT3-ITD gene mutation, all achieved complete remission, and no recurrence occurred in three years. Conclusion:Multiple RT-PCR and gene sequencing technology, quickly detecting associated gene of acute leukemia, plays an important role in acute leukemia diagnosis, prognosis and assessment, and furthermore it can be used to monitor minimal residual disease and to guide clinical individualized treatment.

参考文献：

[1] KIM M J,CHO S Y,LEE W I,et al.The utility of the multiplex reverse transcriptase polymerase chain reaction assay in the detection of hematologic malignancies[J].Ann Lab Med,2013,33(4):304-307.
[2] 李静,殷献录,刘桂玲,等.抑癌基因PTEN在急性白血病发病中临床意义的探讨[J].东南大学学报(医学版),2010,29(1):77-80.
[3] PALLISGAARD N,HORLAND P,RⅡSHOJ D C,et al.Multiplex reverse transcription polyymerase chain reaction for simultaneous screening of 29 translocations and chromosomal aberrations in acute leukemia[J].Blood,1998,92(2):574-588.
[4] SEONG PARK J,CHOI J H,KANG S Y,et al.Clinical significance of cryptic chromosomal translocations detected by multiplex RT-PCR in patients with acute leukemia[J].Int J Lab Hematol,2014,36(1):e20-e23.
[5] OLESEN L H,CLAUSEN N,DIMITRIJEVIC A,et al.Prospective application of a multiplex reverse transcription-polymerase chain reaction assay for the detection of balanced translocations in leukaemia:a single-laboratory study of 390 paediatric and adult patients[J].Br J Haematol,2004,127(1):59-66.
[6] CHUNG C,MA H.Driving toward precision medicine for acute leukemias:are we there yet?[J].Pharmacotherapy,2017,37(9):1052-1072.
[7] CHO Y U,CHI H S,PARK C J,et al.Rapid detection of prognostically significant fusion transcripts in acute leukemia using simplified multiplex reverse transcription polymerase chain reaction[J].J Korean Med Sci,2012,27(10):1155-1161.
[8] MROZEK K,HEEREMA N A,BLOOMFIELD C D.Cytogenetics in acute leukemia[J].Blood Rev,2004,18(2):115-136.
[9] DOHNER H,ESTEY E H,AMADORI S,et al.Diagnosis and management of acute myeloid leukemia in adults:recommendations from an international expert panel,on behalf of the European LeukemiaNet[J].Blood,2010,115(3):453-474.
[10] CORNELISSEN J J,GRATWOHL A,SCHLENK R F,et al.The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission:an integrated-risk adapted approach[J].Nat Rev Clin Oncol,2012,9(10):579-590.

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