Next Article in Journal
Cancer Nanomedicine
Next Article in Special Issue
Proteotoxic Stress and Cell Death in Cancer Cells
Previous Article in Journal
Oncologic Benefit of Adjuvant Chemoradiation after D2 Gastrectomy: A Stepwise Hierarchical Pooled Analysis and Systematic Review
Article

Relation of Neutrophil Gelatinase-Associated Lipocalin Overexpression to the Resistance to Apoptosis of Tumor B Cells in Chronic Lymphocytic Leukemia

1
Cell Death and Drug Resistance in Lymphoproliferative Disorders Team, Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université de Paris, F-75006 Paris, France
2
Biological Hematology Department, Hospital Group Pitié-Salpêtrière, F-75013 Paris, France
*
Author to whom correspondence should be addressed.
Senior co-authorship.
These authors contributed equally to this work.
Cancers 2020, 12(8), 2124; https://doi.org/10.3390/cancers12082124
Received: 19 June 2020 / Revised: 22 July 2020 / Accepted: 27 July 2020 / Published: 31 July 2020
(This article belongs to the Special Issue Deregulation of Cell Death in Cancer)
The resistance to apoptosis of chronic lymphocytic leukemia (CLL) cells partly results from the deregulated production of survival signals from leukemic cells. Despite the development of new therapies in CLL, drug resistance and disease relapse still occur. Recently, neutrophil gelatinase-associated lipocalin (NGAL), a secreted glycoprotein, has been suggested to have a critical role in the biology of tumors. Thus, we investigated the relevance of NGAL in CLL pathogenesis, analyzed the expression of its cellular receptor (NGAL-R) on malignant B cells and tested whether CLL cells are resistant to apoptosis through an autocrine process involving NGAL and NGAL-R. We observed that NGAL concentrations were elevated in the serum of CLL patients at diagnosis. After treatment (and regardless of the therapeutic regimen), serum NGAL levels normalized in CLL patients in remission but not in relapsed patients. In parallel, NGAL and NGAL-R were upregulated in leukemic cells from untreated CLL patients when compared to normal peripheral blood mononuclear cells (PBMCs), and returned to basal levels in PBMCs from patients in remission. Cultured CLL cells released endogenous NGAL. Anti-NGAL-R antibodies enhanced NGAL-R+ leukemia cell death. Conversely, recombinant NGAL protected NGAL-R+ CLL cells against apoptosis by activating a STAT3/Mcl-1 signaling pathway. Our results suggest that NGAL and NGAL-R, overexpressed in untreated CLL, participate in the deregulation of the apoptotic machinery in CLL cells, and may be potential therapeutic clues for CLL treatment. View Full-Text
Keywords: apoptosis; CLL; Mcl-1; NGAL; NGAL-R; relapse; remission; STAT3; survival apoptosis; CLL; Mcl-1; NGAL; NGAL-R; relapse; remission; STAT3; survival
Show Figures

Graphical abstract

MDPI and ACS Style

Bauvois, B.; Pramil, E.; Jondreville, L.; Chapiro, E.; Quiney, C.; Maloum, K.; Susin, S.A.; Nguyen-Khac, F. Relation of Neutrophil Gelatinase-Associated Lipocalin Overexpression to the Resistance to Apoptosis of Tumor B Cells in Chronic Lymphocytic Leukemia. Cancers 2020, 12, 2124. https://doi.org/10.3390/cancers12082124

AMA Style

Bauvois B, Pramil E, Jondreville L, Chapiro E, Quiney C, Maloum K, Susin SA, Nguyen-Khac F. Relation of Neutrophil Gelatinase-Associated Lipocalin Overexpression to the Resistance to Apoptosis of Tumor B Cells in Chronic Lymphocytic Leukemia. Cancers. 2020; 12(8):2124. https://doi.org/10.3390/cancers12082124

Chicago/Turabian Style

Bauvois, Brigitte, Elodie Pramil, Ludovic Jondreville, Elise Chapiro, Claire Quiney, Karim Maloum, Santos A. Susin, and Florence Nguyen-Khac. 2020. "Relation of Neutrophil Gelatinase-Associated Lipocalin Overexpression to the Resistance to Apoptosis of Tumor B Cells in Chronic Lymphocytic Leukemia" Cancers 12, no. 8: 2124. https://doi.org/10.3390/cancers12082124

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop