Analysis of bone marrow supernatant neutrophil gelatinase‐associated lipocalin and hematological parameters in hematological malignancy

Abstract

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a urine biomarker related to acute renal injury. Whereas several studies have evaluated NGAL levels in hematological malignancy, using peripheral blood (PB). Recently, bone marrow (BM) NGAL level was reported to be higher than PB NGAL level in individuals with hematological malignancy, suggesting that BM NGAL would reflect BM microenvironment better than PB NGAL. We measured BM NGAL levels in patients with hematological malignancy, comparing those with NGAL levels in normal BM. We evaluated the association of BM NGAL with hematological parameters including neutrophil counts.Methods: BM samples were collected from 107 patients who underwent BM examination. Immunoassays were used to assess NGAL levels. Data on hematological parameters were collected from medical records. Intergroup comparisons were performed using the Kruskal-Wallis H test and Pearson chi-square test. Single and multiple regression analyses were performed to analyze the relationships. Results:The independent factors that affected the BM NGAL level were neutrophil counts and BM band neutrophil%, while neutrophil count was the main influencing factor. The acute myeloid leukemia (n = 18) and myelodysplastic syndrome (n = 25) groups showed statistically lower BM NGAL levels than patients with normal BM.The myeloproliferative neoplasm group (n = 34) showed higher BM NGAL levels than patients with normal BM, but this difference was not statistically significant.Neutrophil counts and BM band neutrophil% showed intergroup patterns similar to those of BM NGAL levels. Conclusion:BM NGAL was related to neutrophil count and BM band neutrophil%, showing different levels according to hematological malignant disease entities.

Analysis of the Relationship between the Expression Levels of Neutrophil Gelatinase-Associated Lipocalin and Cytokine Genes in Bone Marrow

“…Hb, neutrophil counts, platelet counts, and NGAL normalized counts were significantly lower in the AML and MDS groups than in the MPN group (Table 1 ; Supplementary Table S1 ). NGAL normalized counts showed a pattern similar to BM NGAL protein levels in previous studies 8 , 10 .…”

“…As for low NGAL, a previous study using BM supernatant showed that AML group had low NGAL and high CRP levels 8 . That study suggested that the reason to low NGAL levels in AML group would be due to neutrophils or neutrophilic precursors as synthesis and storage sites of NGAL being suppressed by increased leukemic cells 8 .…”

“…Patients were classified into myeloproliferative neoplasm (MPN), AML, and MDS groups based on the WHO diagnostic criteria, after the BM smear and pathological review. The control group (n=9) consisted of patients with lymphoma without BM involvement (n=7) or normocellular marrow without hematological malignancy (n=2) 8 , 9 . None of the patients manifested symptoms of active infections, inflammatory diseases, or kidney failure 7 .…”

“…A few studies measuring NGAL protein levels in the bone marrow (BM) of patients with hematological cancer reported that NGAL levels were significantly lower in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) than in controls 8 - 10 . Given that neutrophilic precursors are the major source of NGAL synthesis and these exist primarily in the BM but not the peripheral blood, such studies have enabled an accurate comparative analysis of NGAL levels according to the hematological malignant disease entity 8 .…”

The Unfolded Protein Response Is a Major Driver of LCN2 Expression in BCR–ABL- and JAK2V617F-Positive MPN

“…On the contrary, MPO did not correlate with LCN2 expression, which might be explained by the fact that the analyzed cell fraction (mononuclear cells separated by density gradient centrifugation) excludes terminally differentiated granulocytic cells. Some very recent studies on different hematological malignancies reported that LCN2 protein strongly correlates with neutrophil count in PB and BM [28] and differs with diagnosis [29]. Of note, the markers used in this study are not sufficiently specific to determine exact cell populations expressing LCN2, as they may also differ from patient to patient.…”