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Detection of minimal residual disease in acute myeloid leukemia

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Abstract

Acute myeloid leukemia (AML) is a curable malignancy, but its cure rate remains disappointingly low. Accurate quantitation of residual AML cells would allow individualization of therapy and thereby increase the likelihood of cure for each patient. Techniques that are being studied for residual disease detection include molecular assays for abnormalities that are present in subsets of AML patients, and multiparameter flow cytometry, which has broader applicability. Although significant advances have been made in the development of assays for monitoring residual disease, and particularly in techniques for molecular quantitation, additional refinement and validation are needed before these assays can be applied routinely in clinical management.

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References

  1. Strehl S, König M, Mann G, Haas OAL: Multiplex reverse transcriptase-polymerase chain reaction screening in childhood acute myeloblastic leukemia. Blood 2001, 97:805–808.

    Article  PubMed  CAS  Google Scholar 

  2. Jurcic JG, Nimer SD, Scheinberg DA, et al.: Prognostic significance of minimal residual disease detection and PML/RARa isoform type: long-term follow-up in acute promyelocytic leukemia. Blood 2001, 98:2651–2656. A series of patients studied by qualitative RT-PCR, with long-term follow-up.

    Article  PubMed  CAS  Google Scholar 

  3. Gameiro P, Vieira S, Carrara P, et al.: The PML-RARa transcript in long-term follow-up of acute promyelocytic leukemia patients. Haematologica 2001, 86:577–585.

    PubMed  CAS  Google Scholar 

  4. Tobal K, Moore H, Macheta M, Yin JAL: Monitoring minimal residual disease and predicting relapse in APL by quantitating PML-RARalpha transcripts with a sensitive competitive RT-PCR method. Leukemia 2001, 15:1060–1065. Residual disease was studied by competitive RT-PCR.

    Article  PubMed  CAS  Google Scholar 

  5. Slack JL, Bi W, Livak KJ, et al.: Pre-clinical validation of a novel, highly sensitive assay to detect PML-RARalpha mRNA using real-time reverse-transcription polymerase chain reaction. J Mol Diagn 2001, 3:141–149.

    PubMed  CAS  Google Scholar 

  6. Tobal K, Newton J, Macheta M, et al.: Molecular quantitation 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. Residual disease was studied by competitive RT-PCR.

    PubMed  CAS  Google Scholar 

  7. Varella-Garcia M, Hogan CJ, Odom LF, et al.: Minimal residual disease (MRD) in remission t(8;21) AML and in vivo differentiation detected by FISH and CD34+ cell sorting. Leukemia 2001, 15:1408–1414.

    Article  PubMed  CAS  Google Scholar 

  8. Miyamoto T, Nagafuji K, Akashi K, et al.: Persistence of multipotent progenitors expressing AML1/ETO transcripts in longterm remission patients with t(8;21) acute myelogenous leukemia. Blood 1996, 87:4789–4796.

    PubMed  CAS  Google Scholar 

  9. Miyamoto T, Weissman IL, Akashi K: AML1/ETO-expressing nonleukemic stem cells in acute myelogenous leukemia with 8;21 chromosomal translocation. Proc Natl Acad Sci U S A 2000, 97:7521–7526.

    Article  PubMed  CAS  Google Scholar 

  10. Wattjes MP, Krauter J, Nagel S, et al.: Comparison of nested competitive RT-PCR and real-time RT-PCR for the detection and quantification of AML1/MTG8 fusion transcripts in t(8;21) positive acute myelogenous leukemia. Leukemia 2000, 14:329–335. This paper compares quantitation of AML1/MTG8 fusion transcripts by competitive and real-time RT-PCR.

    Article  PubMed  CAS  Google Scholar 

  11. Marcucci G, Caligiuri MA, Dohner H, et al.: Quantification of CBFbeta/MYH11 fusion transcript by real time RT-PCR in patients with INV(16) acute myeloid leukemia. Leukemia 2001, 15:1072–1080. Posttreatment CBF β/MYH11 transcript copy numbers predictive of continued remission and relapse were defined.

    Article  PubMed  CAS  Google Scholar 

  12. Krauter J, Hoellge W, Wattjes MP, et al.: Detection and quantification of CBFB/MYH11 fusion transcripts in patients with inv(16)-positive acute myeloblastic leukemia by real-time RT-PCR. Genes Chromosomes Cancer 2001, 30:342–348.

    Article  PubMed  CAS  Google Scholar 

  13. Buonamici S, Ottoviani E, Testoni N, et al.: Real-time quantitation of minimal residual disease in inv(16)-positive acute myeloid leukemia may indicate risk for clinical relapse and may identify patients in a curable state. Blood 2002, 99:443–449. CBF β-MYH11/ABL RNA ratio thresholds predictive of continued remission and of relapse were defined.

    Article  PubMed  CAS  Google Scholar 

  14. Meshinchi S, Woods WG, Stirewalt DL, et al.: Prevalence and prognostic significance of FLT3 internal tandem duplication in pediatric acute myeloid leukemia. Blood 2001, 97:89–94. FLT3 internal tandem duplications were present in 16.5% of children with AML, and were an adverse prognostic factor for remission rate and disease-free and overall survival.

    Article  PubMed  CAS  Google Scholar 

  15. Kottaridis PD, Gale RE, Frew ME, et al.: The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood 2001, 98:1752–1759. FLT3 internal tandem duplications were present in 27% of younger adult AML patients, and were an adverse prognostic factor for diseasefree and overall survival.

    Article  PubMed  CAS  Google Scholar 

  16. Stirewalt DL, Kopecky KJ, Meshinchi S, et al.: FLT3, RAS, and TP53 mutations in elderly patients with acute myeloid leukemia. Blood 2001, 97:3589–3595. FLT3 internal tandem duplications were present in 34% of older adult AML patients.

    Article  PubMed  CAS  Google Scholar 

  17. Stirewalt DL, Willman CL, Radich JP: Quantitative, real-time polymerase chain reactions for FLT3 internal tandem duplications are highly sensitive and specific. Leuk Res 2001, 25:1085–1088. This paper reports an initial attempt at developing a technique for residual disease studies based on presence of FLT3 internal tandem duplication.

    Article  PubMed  CAS  Google Scholar 

  18. Roberts WM, Estrov Z, Ouspenskaia MV, et al.: Measurement of residual leukemia during remission in childhood acute lymphoblastic leukemia. N Engl J Med 1997, 336:317–323.

    Article  PubMed  CAS  Google Scholar 

  19. Inoue K, Ogawa H, Yamagami T, et al.: Long-term follow-up of minimal residual disease in leukemia patients by monitoring WT1 (Wilms tumor gene) expression levels. Blood 1996, 88:2267–2278.

    PubMed  CAS  Google Scholar 

  20. Kreuzer KA, Saborowski A, Lupberger J, et al.: Fluorescent 5′-exonuclease assay for the absolute quantification of Wilms’ tumour gene (WT1) mRNA: implications for monitoring human leukaemias. Br J Haematol 2001, 114:313–318.

    Article  PubMed  CAS  Google Scholar 

  21. Matsushita M, Ikeda H, Kizaki M, et al.: Quantitative monitoring of the PRAME gene for the detection of minimal residual disease in leukaemia. Br J Haematol 2001, 112:916–926.

    Article  PubMed  CAS  Google Scholar 

  22. San Miguel JF, Vidriales MB, Lopez-Berges C, et al.: Early immunophenotypical evaluation of minimal residual disease in acute myeloid leukemia identifies different patient risk groups and may contribute to postinduction treatment stratification. Blood 2001, 98:1746–1751. The level of residual disease detected by multiparameter flow cytometry after induction therapy predicts subsequent outcome.

    Article  PubMed  CAS  Google Scholar 

  23. Venditti A, Buccisano F, Del Poeta G, et al.: Level of minimal residual disease after consolidation therapy predicts outcome in acute myeloid leukemia. Blood 2000, 96:3948–3952. The level of residual disease detected by multiparameter flow cytometry after consolidation therapy predicts subsequent outcome.

    PubMed  CAS  Google Scholar 

  24. Baer MR, Stewart CC, Dodge RK, et al.: High frequency of immunophenotype changes in acute myeloid leukemia at relapse: implications for residual disease detection (Cancer and Leukemia Group B Study 8361). Blood 2001, 97:3574–3580. Immunophenotype changes at relapse are very common in AML and pose an obstacle to residual disease detection by multiparameter flow cytometry.

    Article  PubMed  CAS  Google Scholar 

  25. van der Pol MA, Pater JM, Feller N, et al.: Functional characterization of minimal residual disease for P-glycoprotein and multidrug resistance protein activity in acute myeloid leukemia. Leukemia 2001, 15:1554–1563.

    Article  PubMed  Google Scholar 

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  1. Leukemia Section, Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, 14263, Buffalo, NY, USA

    Maria R. Baer MD

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  1. Maria R. Baer MD
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Baer, M.R. Detection of minimal residual disease in acute myeloid leukemia. Curr Oncol Rep 4, 398–402 (2002). https://doi.org/10.1007/s11912-002-0033-z

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  • DOI: https://doi.org/10.1007/s11912-002-0033-z

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