| BackgroundThe ETV6(previously TEL)gene is a frequent target of deletion and translocation in leukemia.ETV6gene can translocates to many different partner genes and provides diverse roles in leukemogenesis.The ETV6/RUNX1(also known as TEL/AML1)fusion gene results from the chromosomal translocation t(12;21).being the most frequent gene rearrangement in childhood acute lymphoblastic leukemia (ALL). This leukemia subtype in childhood ALL is generally associated with good prognostic parameters and excellent molecular response to treatment.But the associations between ETV6gene translocation and the clinical characteristic and prognosis of adult ALL are presently not definitively clear.ObjectivesThe aim of the study is to investigate the rearrangement of ETV6gene in adult patients with ALL, and analyze the possible relationship between ETV6gene rearrangement and the clinical features and prognosis in such a disease.Meterials and MethodsIn the observed group,32adult patients with ALL (21males and11females,27newly diagnosed and5cases of refractory/relapse disease) were enrolled into the study, with a median age of38years old (range13-64). The diagnosis was based on morphology, immunology, and cytogenetics (MIC) classification. Twenty healthy donors were chosen as controls. Fresh bone marrow was obtained for test. Split-signal fluorescence in situ hybridization (Split-signal FISH) was used to detect the ETV6gene translocation and rearrangement. Briefly, the split-signal FISH approach is using two different labeled probes(green and red) which located at the opposite sides of the breakpoint region on target gene. The gene translocation will result in the separated green and red signals which demonstrate the split signals and gene rearrangement.Nested Reverse transcription-polymerase chain reaction(Nested RT-PCR) was performed for testing the ETV6-RUNX1by using the specific primers, which will confirme the presence of the fusion gene. Clinical and prognositic characteristics were analyzed for the patient presenting ETV6-RUNX1fusion gene.Results①Only one of32ALL patients were demonstrated as having ETV6gene rearrangement in our current study, the positive rate was3.13%. No abnormal ETV6fluorescence signal was detected in the control group.②The ETV6transcript fused to RUNX1which formed ETV6-RUNX1fusion gene were demonstrated by nested RT-PCR reaction in that positivecase, with specific primers and the PCR products separated on a1.0%agarose gel. No ETV6-RUNX1transcript was observed in the control group.③The case which showed a positive ETV6-RUNX1fusion was a34-year-old younger male patient with refractory and relapsed disease, who had a normal karyotype of46XY by conventional cytogenetic analysis(CCA). PCR for routine screen of BCR/ABL,MLL/AF4,MYC/IgH,PBX/E2A translations did not get any positive result. The patient achieved the first complete remission followed the VDLP protocols, but relapse occurred at four months. The patient did not achieved the second remission and died nine months after the initial diagnosis. Three adverse prognostic features were observed at presentation:older age,high white cell count and the Pro-B ALL immunophenotype,and pleiotropic drug resistance were developed after relapsed.ConclusionsETV6-RUNX1fusion gene is rarely occurred in adult ALL. Because of its cryptic nature, the ETV6-RUNX1rearrangement always eludes conventional cytogenetic techniques and yields false-negative results; ETV6-RUNX1translocation may be an implication to a poor outcome in adult ALL patients,especially when combined with the presence of additional adverse prognostic features such as older age and high white cell count,et al; FISH is more sensitive than CCA to detect the presence of minute chromosome rearrangement and fusion gene,Further study is needed to develop a fast and reliable diagnosis strategy that combines the superiorities of G-banded karyotype, FISH, and PCR techniques. |
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