Prognostic value of AML1/ETO fusion transcripts in patients with acute myelogenous leukemia

Cho, Eun Kyung; Jung, Eun Kyung; Ahn, Jeong Yeal; Lim, Do Yoon; Kyung, Sun Young; Ju, Ki Tak; Bang, Soo Mee; Seo, Yiel Hea; Shin, Dong Bok; Lee, Jae Hoon

Abstract

BACKGROUND
The t (8;21) (q22;q22), which produces the fusion gene AML1/ETO, is associated with relatively good prognosis and, in particular, with a good response to cytosine arabinoside. Analysis of t (8;21) positive leukemic blasts has shown characteristic morphological and immunological features. We performed this study to investigate the incidence of AML1/ETO rearrangement in adult AML, especially in M2 subtype, to make a comparison of morphologic, immunophenotypic and clinical characteristics between AML1/ETO rearrangement positive and negative group in patient with AML and to analyze the correlation with other biological parameters.
METHODS
From May 1995 to Sep. 2000, fifty-nine patients with AML including twenty-nine AML-M2 were studied. RNAs were extracted from leukemic cells and reverse transcriptase mediated polymerase chain reaction (RT-PCR) for AML1/ETO fusion transcript was done. Chromosome study, immunophenotypic, and clinical characteristics were analysed and statistical analysis was done.
RESULTS
The male to female ratio was 32:27 in AML and 17:12 in AML-M2. The median age was 43 years (range 14-86) in AML and 43 years (range 14-77) in AML-M2. The incidence of AML1/ETO fusion transcripts was 22.0% in AML and 44.8% in AML-M2. The morphologic finding of bone marrow in AML-M2 showed higher incidence of Auer rods, large blast with prominent golgi and abnormal granules in AML1/ETO positive patients. There was no significant difference of immunophenotype. AML patients with AML1/ETO rearrangement had a tendency of higher complete remission rate (81.8% vs 56.6%, p=0.13). The overall survival (median 82.2 weeks vs 34.4 weeks, p=0.02) and progression free survival (median 50.9 weeks vs 20.4 weeks, p=0.02) of AML1/ETO positive group were longer than those of negative group in AML. AML-M2 patients with AML1/ETO rearrangement had also a tendency of longer overall survival and progression free survival, although there was no significant difference between both group (median OS 82.4 weeks vs 15.6 weeks, p=0.07, median PFS 50.9 weeks vs 16.0 weeks, p=0.09).
CONCLUSION
Our data suggest that AML1/ETO rearrangement is detected frequently in AML, especially M2, and is a favorable prognostic factor. Thus, molecular diagnostic approaches should be used routinely to identify patients with this genetic subtype of AML.