title: Monitoring of minimal residual disease in acute myeloid leukemia with t(8;21)(q22;q22).
abstract: The fusion gene AML1/ETO is a molecular marker for monitoring minimal residual disease (MRD) in acute myeloid leukemia with the t(8;21)(q22;q22) translocation. To evaluate the dynamic variation and prognostic significance of AML1/ETO, bone marrow samples from 52 patients at different periods were examined qualitatively (32 patients) or quantitatively (20 patients) using nested RT-PCR and RQ-PCR, respectively. In the qualitative group, AML1/ETO in 71.88 and 95.45 % patients became negative at six and 24 months after CR, respectively. Patients in long-term remission were all RT-PCR-negative. Patients negative for AML1/ETO at 6-12 months and 12-18 months after CR had lower relapse rate (P = 0.003 and 0.000), higher relapse-free survival (RFS) (P = 0.000 and 0.000), and overall survival (P = 0.001 and 0.000) than patients with positive AML1/ETO. Quantitative analysis showed that there was no trend where higher relapse rate occurred in patients with higher levels of AML1/ETO transcripts at diagnosis (P > 0.05). Patients whose AML1/ETO transcripts decreased by more than 2 log at CR had higher RFS (P = 0.02). At the checkpoints of 3 and 5/6 months after CR, patients with lower AML1/ETO copy numbers showed lower probability of relapse (P = 0.039 and 0.004). An increase of AML1/ETO transcripts (0.5 log) at any time after CR indicated increased risk of relapse (P = 0.002). Our study shows that both qualitative and quantitative detection of AML1/ETO have prognostic value in MRD monitoring. Negative or continuous low expression of AML1/ETO indicates increased disease-free survival.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, People's Republic of China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Zhang
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Bingcheng
authors.initials: B
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Dong
authors.initials: D
authors.lastname: Lin
authors.forename: Chunlin
authors.initials: C
authors.lastname: Zhou
authors.forename: Chengwen
authors.initials: C
authors.lastname: Li
authors.forename: Jianxiang
authors.initials: J
authors.lastname: Wang
authors.forename: Yingchang
authors.initials: Y
authors.lastname: Mi
mesh_terms: D000293:Adolescent; D000328:Adult; D002891:Chromosomes, Human, Pair 21; D002898:Chromosomes, Human, Pair 8; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000175:diagnosis* / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011379:Prognosis; D000075142:RUNX1 Translocation Partner 1 Protein; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein