1. Genetic polymorphisms and expression of NLRP3 inflammasome-related genes are associated with Philadelphia chromosome-negative myeloproliferative neoplasms.
- Author
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Zhou Y, Yan S, Liu N, He N, Zhang A, Meng S, Ji C, Ma D, and Ye J
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Case-Control Studies, Female, Genetic Predisposition to Disease, Humans, Inflammasomes metabolism, Interleukin-1beta genetics, Male, Middle Aged, NF-kappa B p50 Subunit genetics, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Polycythemia Vera metabolism, Primary Myelofibrosis metabolism, Thrombocythemia, Essential metabolism, Young Adult, Gene Expression, Inflammasomes genetics, NLR Family, Pyrin Domain-Containing 3 Protein genetics, Philadelphia Chromosome, Polycythemia Vera genetics, Polymorphism, Single Nucleotide, Primary Myelofibrosis genetics, Thrombocythemia, Essential genetics
- Abstract
Inflammation plays a crucial role in the initiation, progression and prognosis of Philadelphia chromosome-negative myeloproliferative neoplasms (MPN), which could be clinically subdivided into polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Nucleotide binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasomes affect inflammatory diseases and carcinomas by excessive production of cytokines. To investigate a possible association of NLRP3 inflammasome signaling with MPN, we investigated the expression of selected inflammasome-related genes from bone marrow cells of 67 MPN patients as well as gene polymorphisms in NLRP3 (rs35829419), NF-κB1 (rs28362491), CARD8 (rs2043211), IL-1β (rs16944), and IL-18 (rs1946518). It showed that inflammasome-related genes (NLRP3, NF-κB1, CARD8, IL-1β, and IL-18) were highly expressed in BM cells from MPN patients and the increased expression was associated with JAK2
V617F mutation, white blood cell counts and splenomegaly. Analysis of genetic polymorphisms in 269 MPN patients and 291 healthy controls demonstrated that NF-κB1 (rs28362491) was associated with MPN and increased expression of NF-κB1, NLRP3 and IL-1β. This research provided novel biomarkers and potential targets for MPN., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interests regarding the publication of this paper., (Copyright © 2020 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)- Published
- 2020
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