Increased plasma nicotinamide phosphoribosyltransferase is associated with a hyperproliferative phenotype and restrains disease progression in MPN‐associated myelofibrosis

Abstract

Myeloproliferative neoplasm (MPN)-associated myelofibrosis is a clonal, neoplastic disorder of the hematopoietic stem cells, in which inflammation and immune dysregulation play an important role. Extracellular nicotinamide phosphoribosyltransferase (eNAMPT), also known as visfatin, is a cytokine implicated in a number of inflammatory and neoplastic diseases. Here plasma levels of eNAMPT in patients with MPN-associated myelofibrosis and their effects on disease phenotype and outcomes were examined. The concordance of eNAMPT levels with the marker of general inflammation high-sensitivity C-reactive protein (hs-CRP) was also studied. A total of 333 MPN-associated myelofibrosis patients (187 males and 146 females) and 31 age-and gender-matched normal-weight healthy subjects were enrolled in the study main body. Levels of eNAMPT and hs-CRP were simultaneously assayed in 209 MPN-associated myelofibrosis patients. Twenty-four polycythemia vera or essential thrombocythemia patients were used as controls. eNAMPT was over expressed in MPN-associated myelofibrosis, and eNAMPT expression was correlated with higher white blood cell count, higher hemoglobin, and higher platelet count, suggesting that eNAMPT is an indispensable permissive agent for myeloproliferation of MPN-associated myelofibrosis. The lack of correlation between eNAMPT and hs-CRP revealed that eNAMPT in MPN-associated myelofibrosis does not behave as a canonical inflammatory cytokine. In addition, higher levels of eNAMPT predicted longer time to blast transformation, and protected against progression toward thrombocytopenia and large splenomegaly. In conclusion, in MPN-associated myelofibrosis high levels of eNAMPT mark the myeloproliferative potential and, at variance with a high number of cancers, are protective against disease progression.Am. J.

Neutralization of extracellular NAMPT (nicotinamide phosphoribosyltransferase) ameliorates experimental murine colitis

“…All the three cohorts were compared with a group of healthy donors (data not shown). We found for healthy donors a median of 0.28 ng/ml, which is superimposable to what was described previously [37]. As shown in Fig.…”

New Markers of Disease Progression in Myelofibrosis

“…In a paper published by our group [ 105 ], PMF patients were enrolled to verify the association between plasmatic eNAMPT and the phenotype/progression of the disease. In patients with PMF, eNAMPT was fivefold higher than in controls and higher eNAMPT was associated with increasing hemoglobin, leukocytes, and platelet count.…”

“…Results indicate that eNAMPT levels were increased in a huge number of PMF patients and higher levels of eNAMPT mark the disease hyperproliferative potential. Our group [ 105 ] interpreted the association between eNAMPT and the increased number of mature blood cells, hypothesizing that eNAMPT could be essential for myeloproliferation and an important permissive agent for the malignant hematopoietic proliferation and/or differentiation. Moreover, elevated levels of eNAMPT in patients with PMF predicted a slowing of the disease progression toward a worsening phenotype and blast transformation, whereas lower levels were correlated with a briefer interval to blast transformation.…”

Extracellular Nicotinamide Phosphoribosyltransferase as a Surrogate Marker of Prominent Malignant Potential in Colonic Polyps: A 2-Year Prospective Study

“…Namely, similar to eNAMPT, CRC risk is also highly associated with lipid metabolism and inflammation. To date, associations between eNAMPT and oncogenic potential have been uncovered in several cancers, including CRC [ 27 ], esophagogastric junction adenocarcinoma [ 28 ], melanoma [ 29 ], chronic lymphocytic leukemia [ 30 ], myeloproliferative neoplasm-associated myelofibrosis [ 31 ], rhabdomyosarcomas, and leiomyosarcomas [ 32 ]. Therefore, eNAMPT is defined as a new cancer metabokine.…”