The Possible Clinical Significance Of AML1-ETO9a Isoform In Acute Myeloid Leukemia M₂ Subtype With T(8;21)

Rearch Background The t(8;21)(q22;q22) translocation is one of the most non-random common genetic abnormalities in acute myeloid leukemia (AML), and generates AML1-ETO fusion gene. Dong-Er Zhang had confirmed the existence of AML1-ETO9a isoform, and investigated the role of AE and its isoform AE9a in the development of leukemia through the establishment of animal models . Their results showed that the solely expression of AE was insufficient to produce leukemia, while AE9a was more closely correlated to the leukemia occurrence. These two isoforms may play common roles in leukemogenesis. Our previous laboratory study showed that coexpression of AE9a and AE could be found in about 87% t(8;21) positive M2 patients.Objective To study the possible clinical significance of AML1-ETO9a (AE9a) isoform in acute myeloid leukemia M2 subtype with t(8;21) translocation.Methods The AE9a expression levels in 35 t(8;21) positive M2 patients were examined by quantitative real-time reverse transcription polymerase chain reaction. Monitor the alteration of the AE9a ratio in AE9a positive patients during follow-up. 10 cases of normal karyotype AML-M2, 5 cases of chronic myeloid leukemia bone marrow specimens were used as control.Results 1. 32 cases have been detected AE9a isoform from 35 cases diagnosed with t (8; 21) positive AML-M2 patients , accounting for 91.43%. while none of 10 cases of normal karyotype AML-M2 and 5 cases of chronic myeloid leukemia could be detected for AE9a isoform.2. The percentages of the expression level of AE9a and AE in the overall expression value were measured by QRT-PCR in 28 newly diagnosed patients'samples. The median percentages of AE9a versus AE were18.16%versus 81.84%,respectively, indicating a much higher expression level of AE than that of AE9a(P<0.01).3. Both amounts of AE9a and AE transcripts decreased in 28 newly-diagnosed patients after one course of standard chemotherapy. Among them, the percentage of expression level of AE9a increased in 22 patients and declined in 6 patients in comparison with that pretreated. These two groups have been found statistical different (P<0.01). Among 22 patients, 15 cases CR, 6 cases NR ,1 case PR; Among 6 patients, 4 cases CR,1 case NR ,1 case PR. No evident discrepancy in the CR rate has been found between these two groups after one course of standard chemotherapy (P>0.05).4. During follow-up, 6 of 35 patients showed a markedly increased percentage of AE9a expression level. Among them 5 patients relapsed within additional 4 months of follow-up; 1 patient was found to be shifted from AML1-ETO/abl negative to positive , accompanied by low fever and thrombocytopenia (PLT fluctuations at 70 * 109 / L).5. No evident discrepancy has been found in the expression level of AE9a between the one group of Leukocytes> 10 * 109 / L and the other group of Leukocytes<10 * 109 / L(P>0.05).6. No evident discrepancy has been found in the expression level of AE9a between the one group of simple t (8; 21) translocation and the other group of accompanying translocation(P>0.05). Conclusion Coexpression of AE9a and AE could be found in about 91.43% t(8;21) positive M2 patients; The chemotherapy sensitivity of AE9a fused transcript isoform was less than that of AE. AE9a may play a more important role in the etiology and evolvement of t(8;21) positive AML-M2 patients. In newly-diagnosed patients, the expression level of AE9a had no correlation with the high leukocyte count and the accompanying chromosome aberration.Monitoring the alteration of AE9a /AE ratio after the complete remission phase might predict the early relapse of the disease.