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Drug-induced immunophenotypic modulation in childhood ALL: implications for minimal residual disease detection
1Centro Ricerca M Tettamanti, Clinica Pediatrica Università Milano-Bicocca, Ospedale San Gerardo, Via Donizetti 106, 20052 Monza, Milan, Italy.
Abstract:
Assessment of minimal residual disease (MRD) by flow cytometry is considered to be based on the reproducibility of the leukemic immunophenotype detected at diagnosis. However, we previously noticed modulation of surface antigen expression in acute lymphoblastic leukemia (ALL) during the early treatment. Hence, we investigated this in 30 children with B-cell precursor ALL consecutively enrolled in the AIEOP-BFM ALL 2000 protocol. Quantitative expression of seven antigens useful in MRD monitoring was studied at diagnosis and compared to that measured at different time points of remission induction therapy. Downmodulation in the expression of CD10 and CD34 occurred at follow-up. By contrast, upmodulation of CD19, CD20, CD45RA, and CD11a was observed, while the expression of CD58 remained stable. Despite this, we could unambiguously discriminate leukemic cells from normal residual B cells. This holds true when bone marrow (BM) samples from similarly treated T-ALL patients, but not from healthy donors, were used as reference. Our results indicate that immunophenotypic modulation occurs in ALL during the early phases of BFM-type protocols. However, the accuracy of MRD detection by flow cytometry seems not negatively affected if adequate analysis protocols are employed. Investigators should take this phenomenon into account in order to avoid pitfalls in flow cytometric MRD studies.
Insights
Minimal residual disease (MRD) assessment in acute lymphoblastic leukemia (ALL) can be affected by changes in surface antigen expression during treatment. However, flow cytometry remains accurate for detecting leukemia cells if appropriate analysis protocols are used.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Minimal residual disease (MRD) detection by flow cytometry relies on consistent leukemic immunophenotype.
- Surface antigen expression in acute lymphoblastic leukemia (ALL) can change during early treatment phases.
Purpose of the Study:
- To investigate immunophenotypic modulation of surface antigens during early treatment in pediatric B-cell precursor ALL.
- To assess the impact of antigen modulation on the accuracy of MRD detection by flow cytometry.
Main Methods:
- Quantitative analysis of seven key antigens at diagnosis and during remission induction therapy in 30 children with B-cell precursor ALL.
- Comparison of antigen expression patterns between diagnostic and follow-up samples.
Main Results:
- Downmodulation of CD10 and CD34 observed; upmodulation of CD19, CD20, CD45RA, and CD11a; CD58 expression remained stable.
- Leukemic cells were unambiguously distinguishable from normal B cells even with antigen modulation.
- Distinguishing leukemic cells was reliable using bone marrow samples from similarly treated T-ALL patients as a reference.
Conclusions:
- Immunophenotypic modulation is a common occurrence in ALL during early BFM-type treatment protocols.
- Flow cytometric MRD detection accuracy is maintained with appropriate analysis protocols despite antigen modulation.
- Awareness of immunophenotypic modulation is crucial for accurate flow cytometric MRD studies in ALL.
