Genetic polymorphisms and expression of NLRP3 inflammasome-related genes are associated with Philadelphia chromosome-negative myeloproliferative neoplasms.

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 JAK2V617F 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.