Clinical Significance of AML/ETO Fusion Gene mRNA in Acute Myelogenous Leukemia.

Acute myelogenous leukemia (AML) patients with normal-karyotype may have undetected chromosome aberrant that could affect prognosis. Screening for known AML-specific genetic abnormalities using the reverse transcription polymerase chain reaction (RT-PCR) may help in arriving at a more definitive prognosis. And RT-PCR is the most sensitive method to detect Minimal residual disease (MRD). Nested PCR was a frequently used method to amplify AML1-ETO fusion gene. To further comprehend the relationship between AML1-ETO mRNA expression in AML and its clinical significance in Eastern China. We investigated the prevalence of t(8;21) (q22;q22) and AML1/ETO fusion gene in 461 unselected de novo patients with AML by single RT-PCR and compared the results of cytogenetic analysis with these of RT-PCR. The patients’ median age was 29(1–76).

The results were used in diagnosis of 461 de novo leukemic patients, and 70 AML1-ETO-postive patients were followed up. 107 in 461 patients (23.2%) AML1/ETO was detected by RT-PCR. 98 in 461 patients (21.3%) showed t(8;21) (q22;q22) in karyotype analysis. All patients who had t(8;21) (q22;q22) in conventional karyotyping also showed the gene rearrangement in molecular analysis. The results showed that AML1/ETO mRNA could be expressed in cells from AML-M1, AML-M2 and AML-M4 patients. The complete remission rate in AML1/ETO-positive patients was significantly higher than that in AML1-ETO-negative patients (without M3 subtype patients)[80.4% (86/107) vs 70.6% (191/269)]. The AML1-ETO-postive patients who became negative after chemotherapy had an optimistic outcome, but the patients who demonstrated persistence of AML1-ETO mRNA had a poor prognosis. In chemotherapeutic group, patients whose AML1/ETO expression turning from negative (3 cases) or faint positive (1 case) to positive relapsed later. So PCR becoming positive again indicated relapsing. Only 7 was detected in 48 M₂ t(8:21) patients who had been maintaining remission for more than 18 months.

RT-PCR detected the overall AML1-ETO-positive rate in AML was from 6% to 13% in Western country. But our results showed the rate is 23.2%. One reason might be that the patients involved in our observation were younger than those patients involved in other observation group reported.. The other reason, which might be more important, was that the differences between China and Western country in race and region.Our results showed single RT-PCR method was sensitive enough to detect AML1-ETO mRNA. These observations suggest that AML1/ETO mRNA could disappear after chemotherapy or bone marrow transplantation. The patients had a great probability to relapse if the results of RT-PCR are continuously positive or change from negative to positive. So Regular detection is necessary for leukemia patients. We can monitor the minimal residual disease by detecting AML1-ETO mRNA regularly to direct clinical therapy