{"doi":"10.1111/bjh.17382","title":"Relative expansion of CD19‐negative very‐early normal B‐cell precursors in children with acute lymphoblastic leukaemia after CD19 targeting by blinatumomab and CAR‐T cell therapy: implications for flow cytometric detection of minimal residual disease","abstract":"<jats:title>Summary</jats:title><jats:p>CD19‐directed treatment in B‐cell precursor acute lymphoblastic leukaemia (BCP‐ALL) frequently leads to the downmodulation of targeted antigens. As multicolour flow cytometry (MFC) application for minimal/measurable residual disease (MRD) assessment in BCP‐ALL is based on B‐cell compartment study, CD19 loss could hamper MFC‐MRD monitoring after blinatumomab or chimeric antigen receptor T‐cell (CAR‐T) therapy. The use of other antigens (CD22, CD10, CD79a, etc.) as B‐lineage gating markers allows the identification of CD19‐negative leukaemia, but it could also lead to misidentification of normal very‐early CD19‐negative BCPs as tumour blasts. In the current study, we summarized the results of the investigation of CD19‐negative normal BCPs in 106 children with BCP‐ALL who underwent CD19 targeting (blinatumomab, <jats:italic>n</jats:italic> = 64; CAR‐T, <jats:italic>n</jats:italic> = 25; or both, <jats:italic>n</jats:italic> = 17). It was found that normal CD19‐negative BCPs could be found in bone marrow after CD19‐directed treatment more frequently than in healthy donors and children with BCP‐ALL during chemotherapy or after stem cell transplantation. Analysis of the antigen expression profile revealed that normal CD19‐negative BCPs could be mixed up with residual leukaemic blasts, even in bioinformatic analyses of MFC data. The results of our study should help to investigate MFC‐MRD more accurately in patients who have undergone CD19‐targeted therapy, even in cases with normal CD19‐negative BCP expansion.</jats:p>","journal":"British Journal of Haematology","year":2021,"id":597904,"datarank":0.5641800173540344,"base_score":3.7612001156935624,"endowment":3.7612001156935624,"self_citation_contribution":0.5641800173540344,"citation_network_contribution":0.0,"self_endowment_contribution":0.5641800173540344,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":42,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1364999,"name":"Alexandra Semchenkova","orcid":"0000-0002-7082-1694","position":1,"is_corresponding":false},{"id":1531874,"name":"Olga Illarionova","orcid":null,"position":2,"is_corresponding":false},{"id":1531875,"name":"Svetlana Kashpor","orcid":null,"position":3,"is_corresponding":false},{"id":1531876,"name":"Varvara Brilliantova","orcid":null,"position":4,"is_corresponding":false},{"id":271647,"name":"Elena Zakharova","orcid":"0000-0003-0178-7549","position":5,"is_corresponding":false},{"id":1365000,"name":"Elena Zerkalenkova","orcid":"0000-0001-9634-5828","position":6,"is_corresponding":false},{"id":1531877,"name":"Andrea Zangrando","orcid":"0000-0002-9816-2299","position":7,"is_corresponding":false},{"id":1531878,"name":"Natalia Bocharova","orcid":null,"position":8,"is_corresponding":false},{"id":1531879,"name":"Larisa Shelikhova","orcid":null,"position":9,"is_corresponding":false},{"id":1531880,"name":"Yulia Diakonova","orcid":null,"position":10,"is_corresponding":false},{"id":1531881,"name":"Vladimir Zhogov","orcid":null,"position":11,"is_corresponding":false},{"id":1531882,"name":"Rimma Khismatullina","orcid":null,"position":12,"is_corresponding":false},{"id":1531883,"name":"Olga Molostova","orcid":null,"position":13,"is_corresponding":false},{"id":1178442,"name":"Barbara Buldini","orcid":"0000-0001-7285-2390","position":14,"is_corresponding":false},{"id":1531884,"name":"Elena Raykina","orcid":null,"position":15,"is_corresponding":false},{"id":1531885,"name":"Sergey Larin","orcid":null,"position":16,"is_corresponding":false},{"id":1531886,"name":"Yulia Olshanskaya","orcid":null,"position":17,"is_corresponding":false},{"id":1531887,"name":"Natalia Miakova","orcid":null,"position":18,"is_corresponding":false},{"id":1531888,"name":"Galina Novichkova","orcid":null,"position":19,"is_corresponding":false},{"id":1256505,"name":"Michael Maschan","orcid":"0000-0003-1735-0093","position":20,"is_corresponding":false},{"id":1365013,"name":"А. М. Попов","orcid":"0000-0002-0889-6986","position":21,"is_corresponding":false},{"id":1531873,"name":"Ekaterina Mikhailova","orcid":"0000-0002-3450-0498","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Relative expansion of CD19‐negative very‐early normal B‐cell precursors in children with acute lymphoblastic leukaemia after CD19 targeting by blinatumomab and CAR‐T cell therapy: implications for flow cytometric detection of minimal residual disease","abstract":"<jats:title>Summary</jats:title><jats:p>CD19‐directed treatment in B‐cell precursor acute lymphoblastic leukaemia (BCP‐ALL) frequently leads to the downmodulation of targeted antigens. As multicolour flow cytometry (MFC) application for minimal/measurable residual disease (MRD) assessment in BCP‐ALL is based on B‐cell compartment study, CD19 loss could hamper MFC‐MRD monitoring after blinatumomab or chimeric antigen receptor T‐cell (CAR‐T) therapy. The use of other antigens (CD22, CD10, CD79a, etc.) as B‐lineage gating markers allows the identification of CD19‐negative leukaemia, but it could also lead to misidentification of normal very‐early CD19‐negative BCPs as tumour blasts. In the current study, we summarized the results of the investigation of CD19‐negative normal BCPs in 106 children with BCP‐ALL who underwent CD19 targeting (blinatumomab, <jats:italic>n</jats:italic> = 64; CAR‐T, <jats:italic>n</jats:italic> = 25; or both, <jats:italic>n</jats:italic> = 17). It was found that normal CD19‐negative BCPs could be found in bone marrow after CD19‐directed treatment more frequently than in healthy donors and children with BCP‐ALL during chemotherapy or after stem cell transplantation. Analysis of the antigen expression profile revealed that normal CD19‐negative BCPs could be mixed up with residual leukaemic blasts, even in bioinformatic analyses of MFC data. The results of our study should help to investigate MFC‐MRD more accurately in patients who have undergone CD19‐targeted therapy, even in cases with normal CD19‐negative BCP expansion.</jats:p>","is_dataset_classified":null,"base_score":3.7612001156935624,"endowment":3.7612001156935624,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"33715150","pmcid":null,"openalex_id":"https://openalex.org/W3138826711","authors":[],"funders":[{"funder_name":"Russian Foundation for Basic Research","grant_id":"17‐29‐06052","title":null},{"funder_name":"Russian Foundation for Basic Research","grant_id":"18‐29‐09132","title":null}],"total_grants":2,"fwci":3.1211,"citation_percentile":0.94083922,"influential_citations":0,"citation_trend":[{"year":2021,"count":8},{"year":2022,"count":8},{"year":2023,"count":15},{"year":2024,"count":4},{"year":2025,"count":4},{"year":2026,"count":3}],"oa_status":"bronze","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjh.17382","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/bjh.17382","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/bjh.17382","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1111/bjh.17382","host_type":"publisher"},{"url":"https://doi.org/10.1111/bjh.17382","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/33715150","host_type":"repository"},{"url":"http://hdl.handle.net/11577/3393981","host_type":"repository"}],"fields_of_study":["CAR-T cell therapy research","Acute Lymphoblastic Leukemia research","Lymphoma Diagnosis and Treatment"],"mesh_terms":["Child","Child, Preschool","Female","Flow Cytometry","Follow-Up Studies","Humans","Male","Neoplasm Proteins","Precursor B-Cell Lymphoblastic Leukemia-Lymphoma","Immunotherapy, Adoptive","Drug Delivery Systems","Antibodies, Bispecific","Neoplasm, Residual","Antigens, CD19"],"keywords":["Blinatumomab","CD19","Minimal residual disease","Medicine","Chimeric antigen receptor","Antigen","Flow cytometry","B cell","Immunology","T cell","Cancer research","Leukemia","Antibody","Immune system","All","Cd19 Targeting","Cd19-negative Precursors"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-28T14:32:59.040896Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}