The Expression of AML1-ETO9a Isoform in Acute Myeloid Leukemia M₂ Subtype and Its Clinical Significance.

AML-ETO (AE) fusion protein caused by t(8;21) is believed to be involved in the development of AML. Most recent studies using a mouse models indicate that expression of a truncated version of AE by alternative splicing, namely AML1/ETO9a (AE9a), may be more closely related to development of leukemia. To validate the hypothesis, we have studied the expression of AE9a in AML-M2 patients and its prognostic value. The Expression of AE fusion gene and AE9a was detected by using RT-PCR in 40 cases of newly diagnosed patients and 30 cases in complete remission. The expression pattern of these fusion genes in M₂ patients was compared with that in other subtypes of AML, MDS and healthy controls. In addition, we have also examined the expression level of AE and AE9a in 40 cases of M₂ patients during follow-up and analyzed the correlation with clinical manifestations. Our Results demonstrated that 19 of 70 cases of AML-M2 patients simultaneously expressed AE and AE9a while 10 cases expressed only AE; 2 cases expressed AE9a alone; the rest expressed neither. 19 of 40 cases of newly diagnosed patients expressed AE9a (47.5%). Neither 30 AML-M2 cases in complete remission nor the other subtypes of AML, Myelodysplastic syndrome (MDS) and healthy controls expressed AE9a. After treatment by 1–3 course of conventional chemotherapy (MA, DA, DA or AAG regimen), 4 of 19 AE9a positive cases attained complete remission (21%), 7 cases relapsed after relieved (36.8%), 3 cases died after transplantation, 3 cases failed to attained remission and gave up(15.8%), 2 cases lost connection after transplant. While after same conventional chemotherapy, 17 of 21 AE9a negative cases (81%) attained remission, 3 cases(14.3%)relapsed after relieved, 1 case (4.8%) died of giving up treatment after attaining remission. These results confirmed that AE9a was closely related to AML-M2, and it may promote the development of leukemia in combination with AE fusion gene. The remission rate in AML1/ETO9a positive patients is remarkable lower than that in negative’s. Thus AE9a expression may indicate an unfavorable prognosis of AML-M2 patients.