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
| Autor: | Natalia Miakova, Sergey Larin, Galina Novichkova, Rimma Khismatullina, Elena Zerkalenkova, Natalia Bocharova, Larisa Shelikhova, Andrea Zangrando, Vladimir Zhogov, Alexander Popov, Elena Raykina, Barbara Buldini, Elena Zakharova, Svetlana Kashpor, Yulia Diakonova, Varvara Brilliantova, Olga Illarionova, Ekaterina Mikhailova, Yulia Olshanskaya, Michael Maschan, Alexandra Semchenkova, Olga Molostova |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Neoplasm Residual CD19-negative precursors Antigens CD19 CD19 targeting Immunotherapy Adoptive CD19 03 medical and health sciences 0302 clinical medicine Drug Delivery Systems Antigen immune system diseases hemic and lymphatic diseases Precursor B-Cell Lymphoblastic Leukemia-Lymphoma Antibodies Bispecific medicine Humans Child B cell ALL flow cytometry minimal residual disease biology business.industry hemic and immune systems Hematology Minimal residual disease Chimeric antigen receptor Neoplasm Proteins Transplantation medicine.anatomical_structure 030220 oncology & carcinogenesis Child Preschool biology.protein Cancer research Blinatumomab Female Bone marrow business 030215 immunology medicine.drug Follow-Up Studies |
| Popis: | 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, n = 64; CAR-T, n = 25; or both, n = 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. |
| Databáze: | OpenAIRE |
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