Detailed immunophenotyping of B-cell precursors in regenerating bone marrow of acute lymphoblastic leukaemia patients: implications for minimal residual disease detection
Language English Country England, Great Britain Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
28419441
DOI
10.1111/bjh.14682
Knihovny.cz E-resources
- Keywords
- B cells, acute leukaemia, flow cytometry, minimal residual disease,
- MeSH
- Antigens, CD34 metabolism MeSH
- Cell Differentiation physiology MeSH
- Gene Rearrangement, B-Lymphocyte immunology MeSH
- Immunophenotyping methods MeSH
- Bone Marrow physiology MeSH
- Humans MeSH
- Adolescent MeSH
- Precursor B-Cell Lymphoblastic Leukemia-Lymphoma diagnosis immunology physiopathology MeSH
- Child, Preschool MeSH
- Precursor Cells, B-Lymphoid immunology pathology physiology MeSH
- Flow Cytometry MeSH
- Regeneration MeSH
- Neoplasm, Residual MeSH
- Immunoglobulin Heavy Chains immunology MeSH
- Check Tag
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antigens, CD34 MeSH
- Immunoglobulin Heavy Chains MeSH
Flow cytometric detection of minimal residual disease (MRD) in children with B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) requires immunophenotypic discrimination between residual leukaemic cells and B-cell precursors (BCPs) which regenerate during therapy intervals. In this study, EuroFlow-based 8-colour flow cytometry and innovative analysis tools were used to first characterize the immunophenotypic maturation of normal BCPs in bone marrow (BM) from healthy children, resulting in a continuous multiparametric pathway including transition stages. This pathway was subsequently used as a reference to characterize the immunophenotypic maturation of regenerating BCPs in BM from children treated for BCP-ALL. We identified pre-B-I cells that expressed low or dim CD34 levels, in contrast to the classical CD34high pre-B-I cell immunophenotype. These CD34-dim pre-B-I cells were relatively abundant in regenerating BM (11-85% within pre-B-I subset), while hardly present in healthy control BM (9-13% within pre-B-I subset; P = 0·0037). Furthermore, we showed that some of the BCP-ALL diagnosis immunophenotypes (23%) overlapped with CD34-dim pre-B-I cells. Our results indicate that newly identified CD34-dim pre-B-I cells can be mistaken for residual BCP-ALL cells, potentially resulting in false-positive MRD outcomes. Therefore, regenerating BM, in which CD34-dim pre-B-I cells are relatively abundant, should be used as reference frame in flow cytometric MRD measurements.
Cancer Research Centre Salamanca Spain
Department of Immunology Erasmus MC University Medical Centre Rotterdam Rotterdam the Netherlands
Department of Paediatric Haematology and Oncology Zabrze Poland
Department of Paediatrics Leiden University Medical Centre Leiden the Netherlands
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