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. 2020 Jul;98(4):336-347.
doi: 10.1002/cyto.b.21879. Epub 2020 Apr 8.

Increased expression of immune checkpoint programmed cell death protein-1 (PD-1) on T cell subsets of bone marrow aspirates in patients with B-Lymphoblastic leukemia, especially in relapse and at diagnosis

Sang Hyuk Park  1 , Eunkyoung You  2 , Chan-Jeoung Park  3 , Young-Uk Cho  3 , Seongsoo Jang  3 , Ho-Joon Im  4 , Jong-Jin Seo  4 , Han-Seung Park  5 , Jung-Hee Lee  5
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Free article

Increased expression of immune checkpoint programmed cell death protein-1 (PD-1) on T cell subsets of bone marrow aspirates in patients with B-Lymphoblastic leukemia, especially in relapse and at diagnosis

Sang Hyuk Park et al. Cytometry B Clin Cytom. 2020 Jul.
Free article

Abstract

Background: We analyzed expression profiles of immune checkpoint receptors on T cell subsets and ligands on leukemic blasts in patients with B-lymphoblastic leukemia (B-ALL).

Methods: Total 149 bone marrow (BM) samples obtained from 65 B-ALL patients with four different clinical status (41 at diagnosis, 54 in complete remission [CR], 34 in persistence, and 20 in relapse), and 32 BM control samples were prospectively enrolled. Expression of immune checkpoint receptor (programmed cell death protein-1 [PD-1]) on T cell subsets and ligands (PD-L1, PD-L2) on leukemic blasts was evaluated by flow cytometry, and was compared between patient subgroups.

Results: Relapsed patients demonstrated highest PD-1 expression proportion and intensity on CD3+ CD4+ T cells with statistical significance when compared to patients in persistence/CR/BM controls (p = .027/<.001/<.001 and .012/.001/<.001, respectively). Newly diagnosed patients showed significantly lower PD-1 expression proportion on CD3+ CD4+ T cells than relapsed patients (p < .001), but their intensity was not significantly different. Relapsed patients showed significantly higher PD-1 expression proportion and intensity on CD3+ CD8+ T cells than patients in CR/BM controls (p = .022/.045 and .049/.005, respectively), but PD-1 expression status on them were not significantly different between relapsed and newly diagnosed patients. PD-L1/L2 expression on leukemic blasts was not significantly different between patient subgroups.

Conclusions: In BM aspirates from B-ALL patients, PD-1 expression on T-cell subsets is increased at diagnosis, and to a greater extent, at relapse. These data suggest the potential usefulness of PD-1 blockade in the treatment of B-ALL, particularly at relapse.

Keywords: B-lymphoblastic leukemia; T cell subsets; flow cytometry; immune checkpoint PD-1.

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