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AACR 2022: Could the NLRP3 Pathway Play a Role in Immune Response in Patients With AML?

By: Joseph Fanelli
Posted: Friday, April 15, 2022

Understanding the remodeling of bone marrow and mesenchymal stem cells, leukemia target, and immune cell dynamics through regulation of the NLRP3 pathway in stromal microenvironments may provide crucial information about the therapeutic modulation of the immune response within the stem cell niche for patients with acute myeloid leukemia (AML), according to findings presented at the American Association for Cancer Research (AACR) Annual Meeting 2022 (Abstract 5608). This analysis on regulating the NLRP3 pathway at phenotypic and genotypic levels revealed a positive correlation between the protein interleukin-1β with the expression of NLRP3, among other findings, according to Jyoti Kode, PhD, of Tata Memorial Center, Mumbai, India, and colleagues.

In this study, the authors analyzed regulation of the NLRP3 pathway by isolating and culturing mesenchymal stem cells from AML bone marrow samples. Samples were chosen that exhibited a heterogeneous fibroblastoid shape.

Multicolor flow cytometry found a high expression of CD90 proteins and a minimal expression of CD45 proteins. Cultured samples of AML bone marrow and mesenchymal stem cells as well as fresh leukemic blasts revealed tunneling nanotubes, increased vesicles, and an increase in mitochondria of irregular shapes and sizes. Microarray data indicated that AML peripheral blood plasma had immunosuppressive effects on healthy peripheral blood mononuclear cells and that natural killer cell cytotoxicity was significantly reduced in the presence of culture supernatant of AML cell lines.

The NLRP3 pathway is stimulated using basic damage-associated molecular pattern agent lipopolysaccharides and secondary activators adenosine 5'-triphosphate or nigericin, the authors found. This activation was visualized by co-localization of NLRP3 and caspase-1, in the presence and absence of NLRP3 inhibitors.

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