Frequency And Clinical Significance In Detection Of ETV6 Gene Rearrangement Among Myelodysplatic Syndrome

ObjectivesTo determine the frequency of ETV6 gene rearrangement among myelodysplastic syndrome.To assess the correlation between the ETV6 gene rearrangement and clinical feature in myelodysplastic syndrome.To assess the correlation between the ETV6 gene rearrangement and clinical prognosis among Myelodysplastic Syndrome.To explore the potential mechanisms of ETV6 gene rearrangement on Myelodysplastic Syndrome.Materials and MethodsSixty six newly diagnosed patients (37 females, 29males, mean age 38 years, range 6-84 years) were studied. The diagnosis of Myelodysplastic Syndrome was based on the prieviously described criteria. Fifteen normal healthy volunteers (5 males, 10 females) between 18 and 35 years (mean 24) were examined as controls.Cytogenetic analysis of bone marrow cells was performed by direct method and/or 24 h culture method. RHG banding was used for karyotype analysis.Split-FISH analysis was performed on the bone marrow samples to detect the gene rearrangement of ETV6. RT-PCR would be perform if we find any t(9; 12)(p24; pl3) case.ResultsThe cytogenetic detected 28 cases with chromosome aberration among the 66 Myelodysplatic Syndrome patients.The results of Split-FISH analysis of the 66 Myelodysplastic Syndrome cases were 8 patients with ETV6 gene rearrangement.ETV6/JAK2 fusion transcript was detected in one patient with t(9;12;22)(p24;p13;q11) by RT-PCR. This is the first report on ETV6/JAK2 fusion in Myelodysplastic Syndrome.The cytogenetic findings and the results of Split-FISH analysis of 66 Myelodysplastic Syndrome cases were 33 patients with chromosome aberration.Ten patients of 33 cases with chromosome aberration transformed to acute myeloid leukemia, while only four patients of 33 cases with normal chromosome transformed to acute myeloid leukemia. It was significantly different contrast between them (p<0.001).ConclusionsThe gene rearrangement of ETV6 is a common target of chromosome translocation involving 12p13, which are associated with Myelodysplastic Syndrome.The gene rearrangement of ETV6 is closely associated with clinical feature and clinical prognosis in Myelodysplastic Syndrome.The HLH domain of ETV6 serves as a dimerization module for the ETV6/JAK2 fusion protein. Dimerzation of the fusion protein leads to the constitutive activation of the protein tyrosine kinase (PTK) domain, autophosphorylation of the fusion protein. The transformation capability of the ETV6/JAK2 fusions is absolutely dependent on the presence and proper function of the HLH and the PTK domains in the fusion protein.Since more than 70% of patients with Myelodysplastic Syndrome have clonal cytogenetic abnormalities, cytogenetic studies and FISH analysis play a pivotal role in defining the concept of primary Myelodysplastic Syndrome and therapy-related Myelodysplastic Syndrome, establishing the diagnosis, evaluating prognosis for survival and transformation to acute myeloid leukemia and approaching the molecular basis of the diseases. Combination of the cytogenetic and FISH analysis may lead to more comprehensive and accurate results.