title: Molecular quantitation of minimal residual disease in acute myeloid leukemia with t(8;21) can identify patients in durable remission and predict clinical relapse.
abstract: One of the most common translocations in acute myeloid leukemia (AML) is the t(8;21), which produces the fusion gene AML1-MTG8. We have developed a sensitive competitive reverse transcriptase-polymerase chain reaction (RT-PCR) assay for AML1-MTG8 transcripts, coupled with a competitive RT-PCR for the ABL transcript as a control to accurately estimate the level of amplifiable RNA. We have shown that AML1-MTG8 and ABL transcripts have equal degradation rates. Thus, this method is useful for multicenter studies. We studied 25 patients with t(8;21) AML by means of serial analysis done on bone marrow (BM) and peripheral blood (PB) samples from 21 patients. Our analysis showed that, in general, a successful induction chemotherapy produces a reduction of 2 to 3 log in the level of AML1-MTG8, followed by a further 2 to 3 log after consolidation/intensification chemotherapy. Levels up to 1 x 10(3) and 1 x 10(2) molecules/microg of RNA in BM and PB, respectively, were compatible with durable remission. On the other hand, 5 patients with levels of 0.71 x 10(5) to 2.27 x 10(5) molecules/microg of RNA in BM and 2.27 x 10(3) to 2.27 x 10(4) molecules/microg of RNA in PB had hematologic relapse within 3 to 6 months. Our data indicate that serial quantitation of AML1-MTG8 transcripts is useful in identifying patients at high risk of relapse and may offer an opportunity for clinical intervention to prevent hematologic relapse. This approach was applied successfully in a patient who had an allogeneic BM transplantation. We also suggest that PB may be used an alternative to BM for quantitating AML1-MTG8 transcripts.
authors.affiliation: University Department of Hematology, Manchester Royal Infirmary, Manchester, United Kingdom. ktobal@labmed.cmht.nwest.rhs.uk
authors.forename: K
authors.initials: K
authors.lastname: Tobal
authors.forename: J
authors.initials: J
authors.lastname: Newton
authors.forename: M
authors.initials: M
authors.lastname: Macheta
authors.forename: J
authors.initials: J
authors.lastname: Chang
authors.forename: G
authors.initials: G
authors.lastname: Morgenstern
authors.forename: P A
authors.initials: PA
authors.lastname: Evans
authors.forename: G
authors.initials: G
authors.lastname: Morgan
authors.forename: G S
authors.initials: GS
authors.lastname: Lucas
authors.forename: J A
authors.initials: JA
authors.lastname: Liu Yin
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001853:Bone Marrow / Q000473:pathology; D002891:Chromosomes, Human, Pair 21 / Q000648:ultrastructure*; D002898:Chromosomes, Human, Pair 8 / Q000648:ultrastructure*; D050676:Core Binding Factor Alpha 2 Subunit; D018572:Disease-Free Survival; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D009364:Neoplasm Recurrence, Local; D018365:Neoplasm, Residual; D015514:Oncogene Proteins, Fusion / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D000075142:RUNX1 Translocation Partner 1 Protein; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014157:Transcription Factors / Q000032:analysis* / Q000235:genetics; D014178:Translocation, Genetic
chemical_list: C107844:AML1-ETO fusion protein, human; D014408:Biomarkers, Tumor; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D000075142:RUNX1 Translocation Partner 1 Protein; D014157:Transcription Factors