TheAML1/ETO fusion gene is expressed in virtually all patients with t(8;21)(q22;q22) acute myelogenous leukemia (AML). Long-term complete remission (CR) of AML with t(8;21) has been observed despite the presence of residualAML1/ ETO fusion transcripts, although detection may depend on the sensitivity of the methods used.We examined a patient with recurrent AML who showed the t(8;21)(q22;q22) chromosomal abnormality following a CR of 15 years.The blast cells at the time of recurrence expressed theAML1/ETO fusion transcript, and the breakpoint of theAML1 gene was located on intron 5. Southern blot analysis of the DNA extracted from bone marrow slides that had been made and stored for 15 years revealed the same rearrangement pattern of theAML1 gene. Furthermore, the junction sequences between theAML1 and theETO genes, analyzed by long-distance inverse polymerase chain reaction, proved to be completely identical. These findings can be interpreted in two ways: (1) The initial leukemia clone persisted and finally relapsed after 15 years in the dormant state. (2) AML developed in different subclones having the sameAML1/ETO junctional sequences but with additional genetic changes (second hit).
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Swirsky DM, Li YS, Matthews JG, Flemans RL, Rees JKH, Hayhoe FGJ. 8;21 translocation in acute granulocytic leukemia: cytological, cytochemical and clinical features.Br J Haematol. 1984;56:199–213.
Berger R, Flandrin G, Bernheim A, et al. Cytogenetic studies on 519 consecutive de novo acute nonlymphocytic leukemias.Cancer Genet Cytogenet. 1987;29:9–21.
Nicifora G, Larson RA, Rowley JD. Persistence of the 8;21 translocation in patients with acute myeloid leukemia type M2 in longterm remission.Blood. 1993;82:712–715.
Downing JR, Head JR, Curcio-Brint AM, et al. An AML1/ETO fusion transcript is consistently detected by RNA-based polymerase chain reaction in acute myelogenous leukemia containing the (8;21)(q22;q22) translocation.Blood. 1993;81:2860–2865.
Miyoshi H, Kozu T, Shimizu K, et al. The t(8;21) translocation in acute myeloid leukemia results in production of an AML1-MTG8 fusion transcript.EMBO J. 1993;7:2715–2721.
Frank R, Zhang J, Uchida H, Meyers S, Hiebert SW, Nimer SD. The AML1/ETO fusion protein blocks transactivation of the GM-CSF promoter by AML1B.Oncogene. 1995;11:2667–2674.
Meyers S, Lenny N, Hiebert SW. The t(8; 21) fusion protein interferes with AML-1B-dependent transcriptional activation.Mol Cell Biol. 1995;15:1974–1982.
Burel SA, Harakawa N, Zhou L, Pabst T, Tenen DG, Zhang D-E. Dichotomy of AML1-ETO functions: growth arrest versus block of differentiation.Mol Cell Biol. 2001;16:5577–5590.
Appelbaum FR, Kopecky KJ. Long-term survival after chemotherapy for acute myeloid leukemia: the experience of the Southwest Oncology Group.Cancer. 1997;80(suppl):2199–2204.
Miyamoto T, Nakafuji K, Akashi K, et al. Persistence of multipotent progenitors expressing AML1/ETO transcripts in long-term remission patients with t(8;21) acute myelogenous leukemia.Blood. 1996;87:4789–4796.
Jurlander J, Caligiuri MA, Ruutu T, et al. Persistence of the AML1/ ETO fusion transcript in patients treated with bone marrow transplantation for t(8;21) leukemia.Blood. 1996;88:2183–2191.
Tobel K, Newton J, Macheta M, et al. Molecular quantification of minimal residual disease in acute myeloid leukemia with t(8;21) can identify patients in durable remission and predict clinical relapse.Blood. 2000;95:815–819.
Satake N, Maseki N, Kozu T, et al. Disappearance of AML1-MTG8 (ETO) fusion transcript in acute myeloid leukaemia patients with t(8;21) in long-term remission.Br J Haematol. 1995;91:892–898.
Muto A, Mori S, Matsushita H, et al. Serial quantification of minimal residual disease of t(8;21) acute myelogenous leukemia with RT-competitive PCR assay.Br J Haematol. 1996;95:85–94.
Willis TG, Jadayel DM, Coignet LJA, et al. Rapid molecular cloning of rearrangements of the IGHJ locus using long-distance inverse polymerase chain reaction.Blood. 1997;90:2456–2464.
Akasaka H, Akasaka T, Kurata M, et al. Molecular anatomy of BCL6 translocations revealed by long-distance polymerase chain reaction-based assays.Cancer Res. 2000;60:2335–2341.
Peterson BA, Bloomfield CD. Prolonged maintained remissions of adult acute non-lymphocytic leukemia.Lancet. 1977;2:158–160.
Sauter C, Fehr J, Frick P, Gmuer J, Honegger H, Martz G. Acute myelogenous leukemia: successful treatment of relapse with cytosine arabinoside,VP 16-213, vincristine and vinblastine (A-triple V).Eur J Cancer Clin Oncol. 1982;18:733–737.
Sambrook J, Fritsch EF, Maniatis T.Molecular Cloning: A Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 2001.
Fey MF, Pilkington SP, Summers C, Wainscoat JS. Molecular diag nosis of haematological disorders using DNA from stored bone marrow slides.Br J Haematol. 1987;67:489–492.
Miyoshi H, Shimizu K, Kozu T, Maseki N, Kaneko Y, Ohki M. t(8; 21) breakpoints on chromosome 21 in acute myeloid leukemia are clustered within a limited region of a single gene, AML1.Proc Natl Acad Sci U S A. 1991;88:10431–10434.
Shimizu K, Miyoshi H, Kozu T, et al. Consistent disruption of the AML1 gene occurs within a single intron in the t(8;21) chromosomal translocation.Cancer Res. 1992;52:6945–6948.
Erickson O, Gao J, Chang KS, et al. Identification of breakpoints in t(8;21) acute myelogenous leukemia and isolation of a fusion transcript, AML1/ETO, with similarity toDrosophila segmentation gene, runt.Blood. 1992;80:1825–1831.
Kozu T, Miyoshi H, Shimizu K, et al. Junctions of the AML1/MTG8 (ETO) fusion are constant in t(8;21) acute myeloid leukemia detected by reverse transcription polymerase chain reaction.Blood. 1993;82:1270–1276.
Tighe JE, Daga T, Calabi F. Translocation breakpoints are clustered on both chromosome 8 and chromosome 21 in the t(8;21) of acute myeloid leukemia.Blood. 1993;81:592–596.
Jowitt SN, Yin JA, Saunders MJ. Relapse myelodysplastic clone differs from acute onset clone as shown by X-linked DNA polymorphism patterns in a patient with acute myeloid leukemia.Blood. 1993;82:613–618.
Hayashi Y, Raimondi SC, Behm FG, et al. Two karyotypically independent leukemic clones with the t(8;21) and 11q23 translocation in acute myeloblastic leukemia at relapse.Blood. 1989;73:1650–1655.
Bernstein ML, Esseltine DW, Emond J, Vekemans M. Acute lymphoblastic leukemia at relapse in a child with acute myeloblastic leukemia.Am J Pediatr Hematol Oncol. 1986;8:153–157.
Rhoades KL, Hetherington CJ, Harakawa N, et al. Analysis of the role of AML1-ETO in leukemogenesis, using an inducible transgenic mouse model.Blood. 2000;96:2108–2115.
Lorsbach RB, Downing JR. The role of the AML1 transcription factor in leukemogenesis.Int J Hematol. 2001;74:258–265.
Marcucci G, Livak KI, Bi W, Strout MO, Bloomfield CD, Caligiuri MA. Detection of minimal residual disease in patients with AML1/ ETO-associated acute myeloid leukemia using a novel quantitative reverse transcription polymerase chain reaction assay.Leukemia. 1998;12:1482–1489.
Krauter J, Wattjes MP, Nagel S, et al. Real-time RT-PCR for the detection and quantification of AML1/MTG8 fusion transcripts in t(8;21)-positive AML patients.Br J Haematol. 1999;107:80–85.
Morschhauser F, Cayuela JM, Martini S, et al. Evaluation of minimal residual disease using reverse-transcription polymerase chain reaction in t(8;21) acute myeloid leukemia: a multicenter study of 51 patients.J Clin Oncol. 2000;18:788–794.
Sugimoto T, Das H, Imoto S, et al. Quantification of minimal residual disease in t(8;21)-positive acute myelogenous leukemia patients using real-time quantitative RT-PCR.Am J Hematol. 2000;64:101–106.
Grünewald K, Lyons J, Hansen-Hagge TE, Janssen JWG, Feichtinger H, Bartram CR. Molecular genetic analysis of DNA obtained from fixed, air dried or paraffin embedded sources.Ann Hematol. 1991;62:108–114.
Shibata D, Martin WJ, Arnheim N. Analysis of DNA sequences in forty-year-old paraffin-embedded thin-tissue sections: a bridge between molecular biology and classical histology.Cancer Res. 1988;48:4564–4566.
Merkelbach S, Gehlen J, Handt S, Füzesi L. Novel enzyme immunoassay and optimized DNA extraction for the detection of polymerase-chain-reaction-amplified viral DNA from paraffinembedded tissue.Am J Pathol. 1997;150:1537–1546.
About this article
Cite this article
Tsukamoto, N., Karasawa, M., Tanaka, Y. et al. Recurrence of Acute Myelogenous Leukemia with the SameAML1/ETO Breakpoint as at Diagnosis after Complete Remission Lasting 15 Years: Analysis of Stored Bone Marrow Smears. Int J Hematol 78, 362–369 (2003). https://doi.org/10.1007/BF02983563
- AML1/ETO gene
- Long-term remission
- Acute leukemia
- Bone marrow slides