Imatinib Mesylate Therapy Induces Reduction in Neutrophil Gelatinase-Associated Lipocalin Serum Levels and Increase in Leptin Concentrations in Chronic Myeloid Leukemia Patients in Molecular Remission

Alonci, Andrea; Allegra, Alessandro; Russo, S.; Penna, Giuseppa; Bellomo, Giacomo; D’Angelo, Arianna; Campo, Salvatore; Cannavó, Antonino; Centorrino, Raffaella; Musolino, Caterina

doi:10.1159/000330948

Cited by 12 publications

(11 citation statements)

References 60 publications

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“…These results are in line with previous findings [10] showing that, under IM, all CML patients in molecular remission had a significant increase in leptin compared to baseline. A possible causal relationship between IM intake and leptin modification is further reinforced by the results obtained here after IM withdrawal.…”

Section: Discussionsupporting

confidence: 93%

“…Leptin stimulates hematopoietic stem cells in vitro , regulates differentiation within the myeloid and erythroid cell lineage, and is involved in the growth of hematopoietic malignancies [9]. An increase of leptin in IM treated CML adult patients in molecular remission has recently been observed [10]. Here we evaluated the serum leptin concentrations in young CML patients during IM assumption.…”

Section: Introductionmentioning

confidence: 96%

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Leptin modification in chronic myeloid leukemia patients treated with imatinib: An emerging effect of targeted therapy.

Mariani

Basciani

Giona

et al. 2013

Leukemia Research Reports

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We evaluated serum leptin levels in 9 young chronic myeloid leukemia (CML) patients under imatinib therapy during a long-term follow-up. Body mass index (BMI) and fat mass percentage (%FM) were also measured. Leptin was above the normal range in 8 out of 9 patients. In one case the hormone was below the reference value. All subjects showed a normal BMI, but 3 had a small increase of FM%. One patient recovered the leptin normal value after imatinib suspension. A tendency to leptin normalization in patients switched to an intermittent therapy was also found. This study suggests that imatinib therapy may result in leptin alteration.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 96%

Leptin modification in chronic myeloid leukemia patients treated with imatinib: An emerging effect of targeted therapy.

Mariani

Basciani

Giona

et al. 2013

Leukemia Research Reports

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“…NGAL expression correlates with that of BCR-ABL [46,47]. Serum/plasma levels of MMP-9 and NGAL are significantly higher in CML patients than in healthy individuals [36,46,47,48]. If CML patients achieve complete molecular remission after imatinib therapy, NGAL serum levels fall and are significantly lower than the disease-state value [47,48].…”

Section: Pro-mmp-9 Ngal and Pro-mmp-9/ngal As Leukaemia Biomarkersmentioning

confidence: 99%

Neutrophil Gelatinase-Associated Lipocalin (NGAL), Pro-Matrix Metalloproteinase-9 (pro-MMP-9) and Their Complex Pro-MMP-9/NGAL in Leukaemias

Bouchet

Bauvois

2014

Cancers

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Matrix metalloproteinase (MMP)-9 and neutrophil gelatinase-associated lipocalin (NGAL) have gained attention as cancer biomarkers. The inactive zymogen form of MMP-9 (pro-MMP-9) also exists as a disulphide-linked heterodimer bound to NGAL in humans. Leukaemias represent a heterogeneous group of neoplasms, which vary in their clinical behavior and pathophysiology. In this review, we summarize the current literature on the expression profiles of pro-MMP-9 and NGAL as prognostic factors in leukaemias. We also report the expression of the pro-MMP-9/NGAL complex in these diseases. We discuss the roles of (pro)-MMP-9 (active and latent forms) and NGAL in tumour development, and evaluate the mechanisms by which pro-MMP-9/NGAL may influence the actions of (pro)-MMP-9 and NGAL in cancer. Emerging knowledge about the coexpression and the biology of (pro)-MMP-9, NGAL and their complex in cancer including leukaemia may improve treatment outcomes.

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“…Concentrations of this small peptide increase in several conditions. Soluble NGAL has been shown to increase with bacterial infections, inflammatory and ischemic damage, metabolic disease, kidney disease, drug and pathogen intoxications, and solid and hematological malignancies [9], [10]. Significantly elevated NGAL has also been described in embryo conditions [11], stem cells [12], and as a result of organ transplants [13].…”

Section: Introductionmentioning

confidence: 99%

Neutrophil Gelatinase-Associated Lipocalin Increases HLA-G+/FoxP3+ T-Regulatory Cell Population in an In Vitro Model of PBMC

Manna¹,

Ghinatti²,

Tazzari³

et al. 2014

PLoS ONE

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BackgroundNeutrophil gelatinase-associated lipocalin (NGAL) is emerging as a mediator of various biological and pathological states. However, the specific biological role of this molecule remains unclear, as it serves as a biomarker for many conditions. The high sensitivity of NGAL as a biomarker coupled with relatively low specificity may hide important biological roles. Data point toward an acute compensatory, protective role for NGAL in response to adverse cellular stresses, including inflammatory and oxidative stress. The aim of this study was to understand whether NGAL modulates the T-cell response through regulation of the human leukocyte antigen G (HLA-G) complex, which is a mediator of tolerance.Methodology/Principal FindingsPeripheral blood mononuclear cells (PBMCs) were obtained from eight healthy donors and isolated by centrifugation on a Ficoll gradient. All donors gave informed consent. PBMCs were treated with four different concentrations of NGAL (40–320 ng/ml) in an iron-loaded or iron-free form. Changes in cell phenotype were analyzed by flow cytometry. NGAL stimulated expression of HLA-G on CD4+ T cells in a dose- and iron-dependent manner. Iron deficiency prevented NGAL-mediated effects, such that HLA-G expression was unaltered. Furthermore, NGAL treatment affected stimulation of regulatory T cells and in vitro expansion of CD4+ CD25+ FoxP3+ cells. An NGAL neutralizing antibody limited HLA-G expression and significantly decreased the percentage of CD4+ CD25+ FoxP3+ cells.Conclusions/SignificanceWe provide in vitro evidence that NGAL is involved in cellular immunity. The potential role of NGAL as an immunomodulatory molecule is based on its ability to induce immune tolerance by upregulating HLA-G expression and expansion of T-regulatory cells in healthy donors. Future studies should further evaluate the role of NGAL in immunology and immunomodulation and its possible relationship to immunosuppressive therapy efficacy, tolerance induction in transplant patients, and other immunological disorders.

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Imatinib Mesylate Therapy Induces Reduction in Neutrophil Gelatinase-Associated Lipocalin Serum Levels and Increase in Leptin Concentrations in Chronic Myeloid Leukemia Patients in Molecular Remission

Cited by 12 publications

References 60 publications

Leptin modification in chronic myeloid leukemia patients treated with imatinib: An emerging effect of targeted therapy.

Leptin modification in chronic myeloid leukemia patients treated with imatinib: An emerging effect of targeted therapy.

Neutrophil Gelatinase-Associated Lipocalin (NGAL), Pro-Matrix Metalloproteinase-9 (pro-MMP-9) and Their Complex Pro-MMP-9/NGAL in Leukaemias

Neutrophil Gelatinase-Associated Lipocalin Increases HLA-G+/FoxP3+ T-Regulatory Cell Population in an In Vitro Model of PBMC

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