Clinical Significance Of Detecting ETV6 Gene Abnormality In Leukemia Patients

ObjectivesTo explore the abnormality of ETV6 gene in patients with acute leukemia or chronic leukemia.To explore the potential oncogenic mechanisms of ETV6 gene abnormality in leukemia.To announce initially the relationship of ETV6 gene abnormality and prognosis of leukemia.Materials andMethodsThirty-one newly diagnosed patients (14 males,17 females, mean age 45 years, range 17-76 years)were studied. The diagnosis of acute leukemia or chronic leukemia was based on 2001 WHO classification and thediagnostic criteria.Cytogenetic analysis of bone marrow cells was performed by direct method and/or 24 h culture method. Chromosome abnormality by conventional cytogenetics of R-banding technique.Split-FISH analysis with split probes RH77972 and D12S922 was performed on the bone marrow samples to detect the abnormality of ETV6.Further FISH experiment was performed using chromosome 12 centromere probe in APL patient with part deletion of ETV6 gene.PML/RARαfusion gene was detected by RT-PCR in APL patient with part deletion of ETV6 gene.ResultsBone marrow cells R-banding chromosome karyotype analysis of 31 cases of luekemia patients showed 12 of 31 had chromosome abnormalies, of which 1 case with +12, and the traditional cytogenetic analysis had not found any other chromosome abnormalies of chromosome 12.A APL patient with part deletion of ETV6 was detected by Split-signal FISH, with normal karyotype 46 XX.Further FISH showed two signal in every bone marrow cell.RT-PCR did not detect PML/RARa fusion gene products in sample of this APL patient with part or whole deletion of ETV6.ConclusionsPart deletion of ETV6 was detected in the APL,but this APL was one case without PML/RARa fusion gene, suggesting that it was close relationship between the pathogenesis of APL and the deletion of ETV6.This case APL without PML-RARa but with part deletion of ETV6 was prognosised Myelodysplastic syndrome MDS afert successful APL therapy, and has a bad prognosis. To our knowledge, this is the first time to report t-MDS of APL only with deletion of ETV6 after successful APL therapy. The deletion of ETV6 lead to the ETV6 protein inactive and losing the function of inhibiting tumor, so the myeloid hematopoietic cells proliferate excessively and process to hematological malignancies.Split-signal FISH is a reliable measure to detect abnormality of ETV6 gene. Combination of the cytogenetic and FISH analysis can bring about more comprehensive and accurate results.