Increased serum levels of neutrophil gelatinase-associated lipocalin in patients with essential thrombocythemia and polycythemia vera

Abstract

Neutrophil gelatinaase-associated lipocalin (NGAL) is a glycoprotein bound with matrix metalloproteinase-9 (MMP-9) in human neutrophils, and elevated tissue NGAL expression has been documented in different infectious and inflammatory conditions. Recent evidence suggests that NGAL expression is induced in many types of human cancer. Moreover, NGAL is required for BCR-ABL-induced tumorigenesis. The aim of the present study was to measure serum levels of NGAL in patients with essential thrombocythemia (ET) and polycythemia vera (PV). We also evaluated NGAL levels in patients with ET and PV with and without thrombotic events, to explore a possible correlation of NGAL with platelet and leukocyte activation, and in patients with sepsis. Serum NGAL levels in the study population were significantly higher than in healthy adults and in subjects with sepsis. A correlation between NGAL and the number of white cells and neutrophils was found in patients with PV and ET. NGAL serum levels were not different depending on the presence or not of the JAK2 mutation, and a mutant allele dosage effect was not observed for NGAL levels. Patients with PV and ET with thrombosis did not have significantly higher levels of NGAL. We were unable to demonstrate a significant association between serum NGAL levels and CD11b or CD62 expression. In conclusion, our study reports evidence demonstrating that increased levels of NGAL appear to be a characteristic of patients with PV and ET.

Lipocalin produced by myelofibrosis cells affects the fate of both hematopoietic and marrow microenvironmental cells

“…[32][33][34] In this study, we showed that the levels of LCN2 in the plasmas of MF patients (PMF, PV-MF, and ET-MF) were greater than those present in normal control plasma, findings that extend the observations of others. [10][11][12][13] Furthermore, the LCN2 levels present in the MF plasmas were two-to threefold greater than those observed in patients with proliferative MPNs (PV and ET), providing a possible link between increased LCN2 levels and progression to MF. An inverse relationship between plasma LCN2 levels and hemoglobin levels and platelet counts, but not white blood cell numbers, in MPN patients was observed, suggesting that LCN2 might be related to the development of anemia and thrombocytopenia.…”

“…14 In addition, LCN2 gene expression has been reported to be increased in CD34 1 cells isolated from primary MF (PMF) and polycythemia vera (PV) patients, and LCN2 levels were elevated in the plasma of MPN patients. [10][11][12][13] Furthermore, Kagoya and coworkers demonstrated in a mouse model that JAK2V617F-positive cells elaborate LCN2, which results in DNA damage in neighboring normal cells and cells belonging to the malignant clone by generating reactive oxygen species (ROS). 11 We therefore further examined the role that LCN2 might play in MPNs.…”

“…[3][4][5][6][7][8][9] Recently, neutrophil gelatinase-associated lipocalin (lipocalin-2; LCN2) has been implicated in the pathobiology of myeloproliferative neoplasms (MPNs). [10][11][12][13] LCN2 promotes the proliferation of the malignant clone in chronic myeloid leukemia. 14 In addition, LCN2 gene expression has been reported to be increased in CD34 1 cells isolated from primary MF (PMF) and polycythemia vera (PV) patients, and LCN2 levels were elevated in the plasma of MPN patients.…”

Using NGAL as an Early Diagnostic Test of Acute Kidney Injury

“…It should be stressed once again that NGAL is not an organ-specific marker. The significant limitations of sNGAL measurement as a structural marker of AKI are increased concentrations in patients with lower respiratory tract infections, 17 systemic infections/sepsis, 18 thrombocythemia, polycythemia, 19 and cancers, 20 while uNGAL increases in patients with urinary tract infections 21 as well being above individual baselines in CKDs. 22 The implications of these limitations include false positive or negative results which could lead to failure of timely diagnosis, which of course is the stated purpose of using NGAL as a biomarker for AKI, demonstrating that the addition of quantitative measurement does not add value to clinical decision processes.…”

Neutrophil Gelatinase-Associated Lipocalin: A New Biomarker for COPD Acute Exacerbation

“…However, NGAL had no significant correlation with fibrinogen, leucocyte and sedimentation speed which were other inflammation indicators. In their study, Allegra et al [16] stated a positive correlation between serum NGAL level and leucocyte and neutrophil counts. In another study conducted by Eagan et al [17] a positive relationship between serum NGAL level and neutrophil counts and CRP in patients with stable COPD.In this study, there was a positive relationship between NGAL and leucocyte count.…”