Analysis And Clinical Significance Of ETV6 Rearrangement In Acute Myelogenous Leukemia -M4Eo

ObjectivesTo detect ETV6 rearrangement in acute myelogenous leukemia-M4Eo patients.To explore the potential oncogenic mechanisms of ETV6 gene rearrangement in acute myelogenous leukemia-M4Eo.To announce initially the relationship of ETV6 gene rearrangement and prognosis of acute myelogenous leukemia-M4Eo.Materials and MethodsEleven newly diagnosed patients(6 females,5 males,mean age 25 years,range 13-37 years) were studied.The diagnosis of acute myelogenous leukemia-M4Eo was based on clinical manifestations,blood assay,bone marrow cells morphologic assay,cell chemical test Immunology,cytogenetics,molecular biology and 2001 WHO classification and the diagnostic criteria of AML.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.ETV6/ARG fusion gene was detected by RT-PCR in patient with chromosome translocation between 12p13 and 1q25.Results Bone marrow cells R-banding chromosome karyotype analysis of 11 cases of AML-M4Eo patients showed 6 of 11 had chromosome abnormalies,of which 4 cases with inv(16),2 cases with +22.The traditional cytogenetic analysis had not found any other chromosome abnormalies.A patient with inv(16)was detected of chromosome translocation between 12p13 and 1q25 by Split-signal FISH,karyotype showed 46 XY,inv(16),t(1;12)(q25;p13).RT-PCR approved the presence of ETV6/ARG fusion gene.This is the second case that ETV6/ARG fusion genes are expressed in AML-M4Eo in the world.This patient with ETV6/ARG was not sensitive to chemical therapy,and had a poorer prognosis than the other 3 patients.ConclusionsThe gene rearrangement of ETV6 is a common target of chromosome translocation involving 12p13,which are associated with acute myelogenous leukemia-M4Eo.The novel ETV6/ARG fusion represents another ETV6-tyrosine kinase fusion.The presence of the ETV6/ARG translocation raises the possibility that the resulting fusion protein functions as an oncogene.ETV6/ARG fusion protein might activate a more myeloid differentiation programme and push the cells towards a more myeloid phenotype.It also prevents G-CSF to stimulate myeloid hematopoietic process,blocking myeloid differentiation and maturation.Split-signal FISH is a reliable measure to detect ETV6 gene rearrangement,which can help to diagnose and assess prognosis of hematological malignancies.