Analysis of subpopulations of bone marrow lymphocytes in patients with acute myeloid leukemia: immunological effects of chemotherapy

Abstract

Introduction. Acute myeloid leukemia is one of the most common types of blood cancers with low five-year survival rate and poor prognosis. The gold standard of treatment for this disease is a chemotherapy scheme called «7+3» which stands for a combination of cytarabine and an anthracycline antibiotic, usually daunorubicin. Lymphocytes play a pivotal role in cancer immunosurveillance. In this study, we conducted a detailed analysis of the effects of the «7+3» chemotherapy regimen on bone marrow lymphocytes and examined several parameters of lymphocytes from patients with acute myeloid leukemia.

Aim of the study is to investigate the percentage and phenotypic characteristics of bone marrow lymphocytes in AML patients at different stages of «7+3» chemotherapy course.

Material and methods. Bone marrow aspirate samples were obtained from 61 AML patients. Among them, 16 patients were treated according to the classical «7+3» scheme and had at least two samples before and after therapy. Erythrocyte lysis buffer was used to isolate leukocytes from bone marrow aspirates, then cells were stained with a panel of antibodies, which included anti-CD3-, CD4-, CD8-, CD16-, CD19-, CD45-, CD56- and CD57-antibodies. FACS analysis was performed on a BD Aria II flow cytometer and data were analyzed using FlowJo software.

Results. The ratio of lymphocyte populations changed during the therapy in the group of 16 AML patients. We found out that B cells were extremely sensitive to «7+3» therapy; they were eliminated by the early post-therapeutic period. NK cells began to recover 2-3 weeks after the end of the course of chemotherapy. Within the total group of 61 AML patients the ratio of CD4+/CD8+ T cells was slightly increased, although this parameter stayed within the normal range. 3 patients whose NK cells did not express CD16 were identified, however, this phenotype did not affect the effectiveness of chemotherapy and patient outcomes.

Conclusion. The present study revealed patterns of changes in the ratio of lymphocyte populations and their surface phenotype under the influence of the «7+3» chemotherapy regimen. In addition, the lack of expression of the surface molecule CD16 on the NK cells of some patients was demonstrated.

Keywords:lymphocytes; antitumor immunity; acute myeloid leukemia; immunopharmacology; T cells; NK cells; B cells

For citation: Zhigarev D.I., Khoreva M.V., Campbell K.S., Gankovskaya L.V. Analysis of subpopulations of bone marrow lymphocytes in patients with acute myeloid leukemia: immunological effects of chemotherapy. Immunologiya. 2021; 42 (4): 364-75. DOI: https://doi.org/10.33029/0206-4952-2021-42-4-364-375 (in Russian)

Funding. The study had no sponsor support.

Conflict of interests. The authors declare no conflict of interests.

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