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Published on: March 26, 2018
CD99 expression in T-lineage ALL: implications for flow cytometric detection of minimal residual disease
M N Dworzak1, G Fröschl, D Printz
1Children's Cancer Research Institute, St Anna Children's Hospital, Vienna, Austria. dworzak@ccri.univie.ac.at
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.
Insights
CD99 is a valuable marker for detecting minimal residual disease (MRD) in T-lineage acute lymphoblastic leukemia (T-ALL). Its surface expression offers an advantage over TdT for MRD assessment in T-ALL patients.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- CD99 expression is elevated on immature T cells compared to mature T cells.
- Minimal Residual Disease (MRD) detection is crucial for T-lineage acute lymphoblastic leukemia (T-ALL) treatment monitoring.
- Assessing MRD in T-ALL requires sensitive and specific markers.
Purpose of the Study:
- To evaluate CD99 as a marker for MRD detection in T-ALL.
- To compare the efficacy of CD99 with the established marker TdT for MRD quantification.
- To determine the utility of CD99 in identifying leukemic cells in bone marrow samples.
Main Methods:
- Flow cytometry was used to analyze CD99 expression on leukemic lymphoblasts in diagnostic bone marrow samples from T-ALL patients.
- CD99 expression levels were compared between leukemic cells and normal T lymphocytes within the same samples.
- CD99 and TdT were used to quantify MRD in follow-up samples and compared using four-color flow cytometry.
Main Results:
- Leukemic lymphoblasts in T-ALL samples showed significantly higher CD99 expression (median 7.7 times) than normal T lymphocytes.
- In 85% of cases, CD99 expression on leukemic cells exceeded the normal population's mean + 2 standard deviations.
- CD99 demonstrated comparable performance to TdT in MRD quantification, with CD99 being more suitable in some patients and TdT in others.
- Both markers exhibited low nonspecific background levels in MRD detection.
Conclusions:
- CD99 is a highly informative marker for MRD detection in T-ALL.
- CD99 offers the advantage of surface expression, facilitating its use in flow cytometry-based MRD assessment.
- CD99 serves as a valuable complement to TdT for comprehensive MRD monitoring in T-ALL.