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CD99 expression in T-lineage ALL: implications for flow cytometric detection of minimal residual disease

Abstract

Expression of CD99 is higher on immature than on mature T cells. We postulated that this marker could be used to assess minimal residual disease (MRD) in T-lineage acute lymphoblastic leukemia (T-ALL). In diagnostic bone marrow (BM) samples from 27 children with T-ALL, expression of CD99 on leukemic lymphoblasts by flow cytometry was in median 7.7 times higher than on normal T lymphocytes from within the same sample. In 85% of cases, leukemic MFI values were higher than the mean MFI+2 s.d. of normal populations. We applied CD99 to study MRD in 39 follow-up samples from 15 consecutive T-ALL patients, and compared the results with those obtained with the well-established MRD-marker terminal deoxynucleotidyl transferase (TdT). Either antibody was combined in four-color flow cytometry with CD7, surfaceCD3, and cytoplasmicCD3. We found that CD99 was a valid complement to TdT in quantifying T-ALL MRD. Given a considerable interpatient variability, CD99 could be favorably used in nine patients, and TdT in other five patients. Both approaches showed a similar very low nonspecific background throughout 12 weeks from diagnosis (in median 0.002% of nucleated BM cells in patients with non-T ALL). We conclude that CD99 is a highly informative tool for MRD detection in T-ALL, bearing the advantage of surface expression in contrast to TdT.

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Acknowledgements

This study has been promoted by the International BFM Study Group under the direction of M Schrappe. We thank the participants of the Austrian BFM-Study Group (B Ausserer, FM Fink, H Haas, N Jones, R Jones, W Kaulfersch, G Müller, I Mutz, R Ploier, K Schmitt, O Stöllinger, and C Urban) for their close collaboration in providing BM and PB samples. In this respect, we are also grateful to the oncologists and the laboratory-team of the St Anna Kinderspital (in particular to S Juhasz, R Kornmüller, E Neidhart, and U Stalze). We also thank G Fritsch, D Scharner, C Eichstill, and A Schumich from the department of flow cytometry of the CCRI for continued technical support. We thank G Mann, N Mühlegger, and J Regelsberger from the Austrian BFM Study Group documentation center for providing the clinical data and U Pötschger for help with statistical analyses.

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Dworzak, M., Fröschl, G., Printz, D. et al. CD99 expression in T-lineage ALL: implications for flow cytometric detection of minimal residual disease. Leukemia 18, 703–708 (2004). https://doi.org/10.1038/sj.leu.2403303

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