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Minimal residual disease (MRD) in remission t(8;21) AML and in vivo differentiation detected by FISH and CD34+ cell sorting

Leukemia volume 15, pages 1408–1414 (2001)Cite this article

Abstract

Many patients with t(8;21) AML have residual positive cells during remission. We previously developed D-FISH probes that detect both derivative chromosomes and the normal alleles. In negative controls, only 2/44000 (0.0045%) positive signals were observed. To investigate MRD, we examined specimens from 29 patients who had initially obtained CR. In remission patients, 61% had 1–4/2000 positive cells (0.05–0.19%). Higher frequencies were found in two patients in early relapse and in one patient in early remission. However, a negative test did not exclude relapse. Since false positives were negligible and because most t(8;21) AMLs express CD34, we asked whether cell sorting combined with FISH would increase the sensitivity. In one patient, we observed that 80% of CD34+ cells were t(8;21)+ at 2 months from initial clinical and cytogenetic remission. However, by 5 months the pre- and post-sorted populations contained 0.15% and 0.06% t(8;21) cells, respectively. Whereas essentially all t(8;21) cells in the initial specimen expressed CD34, only 0.6% were subsequently CD34+. These results are consistent with in vitro assays showing that residual t(8;21) cells undergo differentiation. Thus, FISH can identify MRD in a majority of t(8;21) patients and, combined with CD34+ selection, may provide an indirect assessment of the differentiation state of residual t(8;21) cells.

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Acknowledgements

We wish to acknowledge the assistance of the Flow Cytometry and Cytogenetics Cores of the University of Colorado Cancer Center. M Andreeff was supported by NIH PO1 CA 55164.

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Authors and Affiliations

  1. Division of Medical Oncology, University of Colorado Health Sciences and Cancer Centers, Denver, CO, USA

    M Varella-Garcia, CJ Hogan, H Ai, L Chen, RM Gemmill & HA Drabkin

  2. The Children's Hospital and University of Colorado Cancer Center, Denver, CO, USA

    LF Odom

  3. City of Hope National Medical Center, Duarte, CA, USA

    JL Murata-Collins

  4. Department of Dentistry, Sun Yat-sen University of Medical Sciences, Guanzhou, PR China

    H Ai

  5. Genzyme Genetics, Santa Fe, NM, USA

    K Richkind

  6. Fundação Faculdade Federal de Ciências Médicas de Porto Alegre, Porto Alegre, RS, Brazil

    G Paskulin

  7. Department of Hematology, MD Anderson Cancer Center, Houston, TX, USA

    M Andreeff

  8. Laboratoire d'Hematologie, CHU de Poitiers, Poitiers, France

    A Brizard

  9. Colorado Genetics Laboratory and Department of Pathology, Denver, CO, USA

    L McGavran

  10. INSERM U 434, IGM, Paris, France

    R Berger

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  1. M Varella-Garcia
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  2. CJ Hogan
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  8. G Paskulin
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  11. L McGavran
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  12. RM Gemmill
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  14. HA Drabkin
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Varella-Garcia, M., Hogan, C., Odom, L. et al. Minimal residual disease (MRD) in remission t(8;21) AML and in vivo differentiation detected by FISH and CD34+ cell sorting. Leukemia 15, 1408–1414 (2001). https://doi.org/10.1038/sj.leu.2402219

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  • DOI: https://doi.org/10.1038/sj.leu.2402219

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