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. 2023 Jul-Sep;45(3):324-329.
doi: 10.1016/j.htct.2022.05.005. Epub 2022 Jun 17.

Lower expression of NOTCH components in peripheral blood mononuclear cells of allogeneic hematopoietic cell transplant patients

Marcos Paulo Colella  1 , Beatriz Corey Morini  1 , Fernanda Niemann  1 , Matheus Rodrigues Lopes  2 , Sara Olalla Saad  1 , Patricia Favaro  3
Affiliations

Lower expression of NOTCH components in peripheral blood mononuclear cells of allogeneic hematopoietic cell transplant patients

Marcos Paulo Colella et al. Hematol Transfus Cell Ther. 2023 Jul-Sep.

Abstract

Introduction: Chronic graft-versus-host disease (cGvHD) not only remains the main cause of late mortality after allogeneic hematopoietic cell transplant, but also has the capacity of causing severe organ impairment in those who survive. The Notch, a highly conserved ligand-receptor pathway, is involved in many immunological processes, including inflammatory and regulatory responses. Recently, mouse models have shown that the blockage of canonical Notch signaling prevents GvHD.

Objective and method: Due to the lack of data on the Notch pathway in human chronic GvHD, we sought to study the expression of NOTCH components in primary samples of patients who received allo-HCT and presented active cGvHD or a long-term clinical tolerance to cGvHD.

Results: Our results showed a significantly lower expression of NOTCH components in both groups that received allo-HCT, independently of their cGvHD status, when compared to healthy controls.

Conclusion: Moreover, there were no differences in gene expression levels between the active cGvHD and clinically tolerant groups. To our knowledge, this is one of the first studies performed in human primary samples and our data indicate that much remains to be learned regarding NOTCH signaling as a new regulator of GvHD.

Keywords: Allogeneic hematopoietic cell transplant; Chronic graft-versus-host-disease; Notch; Tolerance.

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Conflict of interest statement

Conflicts of interest None.

Figures

Figure 1
Figure 1
Overall survival by group.
Figure 2
Figure 2
Expression of NOTCH components in peripheral blood mononuclear cells in patients who received allo-HCT and control group Quantitative PCR was performed in cDNA from peripheral blood mononuclear cells for NOTCH1 (A), NOTCH2 (B), JAG1(C), JAG2 (D), DLL1 (E) and DLL4 (F) expression Relative expression was normalized by HPRT1 as the reference gene and results were analyzed using 2−ΔΔCT Horizontal lines represent medians The groups: control (n = 13), chronic graft-versus-host disease (cGvHD; n = 9) and tolerant (n = 8) are indicated *p < 005, **p < 001 and *** p < 0001; ANOVA test followed by Bonferroni post-test.
Figure 3
Figure 3
Comparison of lymphocyte and monocyte counts between groups NS: non-significant.
See this image and copyright information in PMC

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References

    1. Clift RA, Buckner CD, Appelbaum FR, Bearman SI, Petersen FB, Fisher LD, et al. Allogeneic marrow transplantation in patients with acute myeloid leukemia in first remission: a randomized trial of two irradiation regimens. Blood. 1990;76(9):1867-71. - PubMed
    1. Lee SJ, Vogelsang G, Flowers ME. Chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2003;9(4):215–233. - PubMed
    1. Radtke F, MacDonald HR, Tacchini-Cottier F. Regulation of innate and adaptive immunity by Notch. Nat Rev Immunol. 2013;13(6):427–437. - PubMed
    1. Durai V, Murphy KM. Functions of murine dendritic cells. Immunity. 2016;45(4):719–736. - PMC - PubMed
    1. Radojcic V, Maillard I. Notch signaling and alloreactivity. Transplantation. 2016 Dec;100(12):2593–2600. - PMC - PubMed

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