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The Clinical Study On Fusion Genes Of Childhood Acute Leukemia By Multiplex RT-PCR

Posted on:2005-06-10Degree:MasterType:Thesis
Country:ChinaCandidate:J Q LiFull Text:PDF
GTID:2144360125466086Subject:Academy of Pediatrics
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Objective To study fusion genes derived from chromosome structural aberrations in childhood acute leukemia and explore its possible significance in diagnosis , treatment ,and prognosis assessment.Methods Bone marrows samples from 91 children with acute leukemia without treatment were detected the expression of fusion gene by multiplex nested RT-PCR and chromosome , immunology clinical data (including 53 children with acute lymphocyte leukemia and 38 children with acute myeloid leukemia).Results Among these 91 patients, 41 cases(45.05%) carried with 13 kinds of fusion genes such as SIL/TAL1, E2A/PBX1, TEL/AML1, MLLex7/AF9 , MLLex8/AF9 , MLLex8/AF10 , MLLex8/AFX , MLLex9/AF6, MLLex9/ELL, MLLex7/AF4, TLS/ERG , AML1/ETO, PML/RARa (L, S, V) . Among 53 patients with ALL, 18(33.96%) cases of carried with 11 kinds of fusion genes . Among 38 patients with AML, 23(60.53%) cases of carried with 4 kinds of fusion genes . One patient with ALL carried with two fusion genes: MLLex7/AF9 and MLLex8/AF9 . One patient with ALL carried with three fusion genes: MLLex9/ELL, MLLex9/AF6, MLLex8/AFX. The activation of oncogene HOX11 was detected in 9 ALL cases and 8 AML cases, with or without other chromosome aberrations in 7 ALL cases , 7 AML cases and 2 ALL cases , 1 AML cases simply. 2 ALL cases with t(12;21) had arrived complete remission(CR) for 2 year. 1 case carried with fusion gene E2A/PBX1 derived from t(1;19) had died of infection during induction therapy. One patient with T-ALL who only be detected the activation of oncogene HOX11 relapsed after complete remission for 6 months, and died in the end because of intractable drug resistance. 1 case with the high riskB-ALL who carried with HOX 11 derived from t(10;ll) has arrived complete remission for 2 years after strong chemotherapy. 1 case with t(9;ll) arrived complete remission(CR) in the 15th day during DOLP induction therapy and has been CR for 14 months. 1 case with TAL1D had arrived complete remission(CR) for 9 months. Among 20 patients carried with t(15;17) or t(8;21), 11 patients who received therapy all arrived CR and no one relapsed. 2 months after rough attainment of CR ,one patient with FAB subtype Ml who was detected the HOX 11 activation died of relapse.Conclusion MIC classification is one popular classification in leukemia . Gene typing is the most precise classification method, It could direct the clinic treatment : patients with TEL/AML1, AMLl/ETO,PML/RARa have favourable prognosis , patients with B-ALL who carried with HOX 11 have favourable prognosis at short term, patients with T-ALL who carried with HOX1 1 and patients with AML who carried with HOX 11 have unfavourable prognosis, patients with MLL have the worst prognosis and need bone marrow transplantion(BMT) or strong chemotherapy. Multiplex nested RT-PCR technique could quickly screen 29 kinds of fusion genes derived from chromosome structural aberrations at the same time, which maybe help us improve the MICM classification, diagnose disease and assess prognosis precisely, direct the choice of treatment and dose of chemotherapy . Applying multiplex nested RT-PCR technique, we could detect the residual leukemic cell of patients who was hi CCR, this technique could be used to detect MRD and be a index of stopping chemotherapy and decide the dose .
Keywords/Search Tags:children, leukemia, fusion gene, Clinical, multiplex RT-PCR
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