VpreB surrogate light chain expression in B-lineage ALL: a report from the Children's Oncology Group
| Autor: | Amanda McCaustland, Chunxu Qu, Brent L. Wood, Stuart S. Winter, Nyla A. Heerema, Gabriela Gheorghe, Andrew J. Carroll, Bridget S. Wilson, Charles G. Mullighan, No'eau Simeona |
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| Rok vydání: | 2021 |
| Předmět: |
Oncology
medicine.medical_specialty Lineage (genetic) Lymphoma B-Cell Immunoglobulin Light Chains Surrogate Population Developmental arrest Biology Immunoglobulin light chain Cog hemic and lymphatic diseases Internal medicine Genotype medicine Humans Stage (cooking) education Child education.field_of_study B-Lymphocytes Precursor Cells B-Lymphoid Hematology Precursor Cell Lymphoblastic Leukemia-Lymphoma Minimal residual disease Burkitt Lymphoma Stimulus Report |
| Zdroj: | Blood Advances |
| ISSN: | 2473-9537 |
| Popis: | Key Points The VpreB component of the SLC is expressed in standard- and high-risk B-ALL.The VpreB may serve as a novel immunotherapeutic target. Visual Abstract Immunotherapies directed against B-cell surface markers have been a common developmental strategy to treat B-cell malignancies. The immunoglobulin heavy chain surrogate light chain (SLC), comprising the VpreB1 (CD179a) and Lamda5 (CD179b) subunits, is expressed on pro- and pre-B cells, where it governs pre–B-cell receptor (BCR)-mediated autonomous survival signaling. We hypothesized that the pre-BCR might merit the development of targeted immunotherapies to decouple “autonomous” signaling in B-lineage acute lymphoblastic leukemia (B-ALL). We used the Children’s Oncology Group (COG) minimal residual disease (MRD) flow panel to assess pre-BCR expression in 36 primary patient samples accrued to COG standard- and high-risk B-ALL studies through AALL03B1. We also assessed CD179a expression in 16 cases with day 29 end-induction samples, preselected to have ≥1% MRD. All analyses were performed on a 6-color Becton-Dickinson flow cytometer in a Clinical Laboratory Improvement Amendment/College of American Pathologist–certified laboratory. Among 36 cases tested, 32 cases were at the pre-B and 4 cases were at the pro-B stages of developmental arrest. One or both monoclonal antibodies (mAbs) showed that CD179a was present in ≥20% of the B-lymphoblast population. All cases expressed CD179a in the end-induction B-lymphoblast population. The CD179a component of the SLC is commonly expressed in B-ALL, regardless of genotype, stage of developmental arrest, or National Cancer Institute risk status. |
| Databáze: | OpenAIRE |
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