Cargando…

Monocyte Subsets and Serum Inflammatory and Bone-Associated Markers in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma

SIMPLE SUMMARY: We investigated the distribution of different subsets of monocytes (Mo) in blood and bone marrow (BM) of newly-diagnosed untreated monoclonal gammopathy of undetermined significance (MGUS), smoldering (SMM) and active multiple myeloma (MM), and its relationship with immune/bone serum...

Descripción completa

Detalles Bibliográficos
Autores principales: Damasceno, Daniela, Almeida, Julia, Teodosio, Cristina, Sanoja-Flores, Luzalba, Mayado, Andrea, Pérez-Pons, Alba, Puig, Noemi, Arana, Paula, Paiva, Bruno, Solano, Fernando, Romero, Alfonso, Matarraz, Sergio, van den Bossche, Wouter B. L., Flores-Montero, Juan, Durie, Brian, van Dongen, Jacques J. M., Orfao, Alberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004952/
https://www.ncbi.nlm.nih.gov/pubmed/33810169
http://dx.doi.org/10.3390/cancers13061454
_version_ 1783672021586018304
author Damasceno, Daniela
Almeida, Julia
Teodosio, Cristina
Sanoja-Flores, Luzalba
Mayado, Andrea
Pérez-Pons, Alba
Puig, Noemi
Arana, Paula
Paiva, Bruno
Solano, Fernando
Romero, Alfonso
Matarraz, Sergio
van den Bossche, Wouter B. L.
Flores-Montero, Juan
Durie, Brian
van Dongen, Jacques J. M.
Orfao, Alberto
author_facet Damasceno, Daniela
Almeida, Julia
Teodosio, Cristina
Sanoja-Flores, Luzalba
Mayado, Andrea
Pérez-Pons, Alba
Puig, Noemi
Arana, Paula
Paiva, Bruno
Solano, Fernando
Romero, Alfonso
Matarraz, Sergio
van den Bossche, Wouter B. L.
Flores-Montero, Juan
Durie, Brian
van Dongen, Jacques J. M.
Orfao, Alberto
author_sort Damasceno, Daniela
collection PubMed
description SIMPLE SUMMARY: We investigated the distribution of different subsets of monocytes (Mo) in blood and bone marrow (BM) of newly-diagnosed untreated monoclonal gammopathy of undetermined significance (MGUS), smoldering (SMM) and active multiple myeloma (MM), and its relationship with immune/bone serum-marker profiles. Our results showed decreased production of BM Mo with decreased counts of classical Mo (cMo) in BM and blood of SMM and MM, but not MGUS. Conversely, intermediate and non-classical Mo were significantly increased in MGUS, SMM and MM BM. In parallel, increased levels of interleukin (IL)1β were observed in a fraction of MGUS and SMM, while increased serum IL8 was characteristic of SMM and MM, and higher serum IL6, RANKL and bone alkaline phosphatase concentrations, together with decreased counts of FcεRI(+)cMo, were restricted to MM presenting with bone lesions. These results provide new insights in the pathogenesis of plasma cell neoplasms and the potential role of FcεRI(+)cMo in normal bone homeostasis. ABSTRACT: Background. Monocyte/macrophages have been shown to be altered in monoclonal gammopathy of undetermined significance (MGUS), smoldering (SMM) and active multiple myeloma (MM), with an impact on the disruption of the homeostasis of the normal bone marrow (BM) microenvironment. Methods: We investigated the distribution of different subsets of monocytes (Mo) in blood and BM of newly-diagnosed untreated MGUS (n = 23), SMM (n = 14) and MM (n = 99) patients vs. healthy donors (HD; n = 107), in parallel to a large panel of cytokines and bone-associated serum biomarkers. Results: Our results showed normal production of monocyte precursors and classical Mo (cMo) in MGUS, while decreased in SMM and MM (p ≤ 0.02), in association with lower blood counts of recently-produced CD62L(+) cMo in SMM (p = 0.004) and of all subsets of (CD62L(+), CD62L(−) and FcεRI(+)) cMo in MM (p ≤ 0.02). In contrast, intermediate and end-stage non-classical Mo were increased in BM of MGUS (p ≤ 0.03), SMM (p ≤ 0.03) and MM (p ≤ 0.002), while normal (MGUS and SMM) or decreased (MM; p = 0.01) in blood. In parallel, increased serum levels of interleukin (IL)1β were observed in MGUS (p = 0.007) and SMM (p = 0.01), higher concentrations of serum IL8 were found in SMM (p = 0.01) and MM (p = 0.002), and higher serum IL6 (p = 0.002), RANKL (p = 0.01) and bone alkaline phosphatase (BALP) levels (p = 0.01) with decreased counts of FcεRI(+) cMo, were restricted to MM presenting with osteolytic lesions. This translated into three distinct immune/bone profiles: (1) normal (typical of HD and most MGUS cases); (2) senescent-like (increased IL1β and/or IL8, found in a minority of MGUS, most SMM and few MM cases with no bone lesions); and (3) pro-inflammatory-high serum IL6, RANKL and BALP with significantly (p = 0.01) decreased blood counts of immunomodulatory FcεRI(+) cMo-, typical of MM presenting with bone lesions. Conclusions: These results provide new insight into the pathogenesis of plasma cell neoplasms and the potential role of FcεRI(+) cMo in normal bone homeostasis.
format Online
Article
Text
id pubmed-8004952
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-80049522021-03-29 Monocyte Subsets and Serum Inflammatory and Bone-Associated Markers in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma Damasceno, Daniela Almeida, Julia Teodosio, Cristina Sanoja-Flores, Luzalba Mayado, Andrea Pérez-Pons, Alba Puig, Noemi Arana, Paula Paiva, Bruno Solano, Fernando Romero, Alfonso Matarraz, Sergio van den Bossche, Wouter B. L. Flores-Montero, Juan Durie, Brian van Dongen, Jacques J. M. Orfao, Alberto Cancers (Basel) Article SIMPLE SUMMARY: We investigated the distribution of different subsets of monocytes (Mo) in blood and bone marrow (BM) of newly-diagnosed untreated monoclonal gammopathy of undetermined significance (MGUS), smoldering (SMM) and active multiple myeloma (MM), and its relationship with immune/bone serum-marker profiles. Our results showed decreased production of BM Mo with decreased counts of classical Mo (cMo) in BM and blood of SMM and MM, but not MGUS. Conversely, intermediate and non-classical Mo were significantly increased in MGUS, SMM and MM BM. In parallel, increased levels of interleukin (IL)1β were observed in a fraction of MGUS and SMM, while increased serum IL8 was characteristic of SMM and MM, and higher serum IL6, RANKL and bone alkaline phosphatase concentrations, together with decreased counts of FcεRI(+)cMo, were restricted to MM presenting with bone lesions. These results provide new insights in the pathogenesis of plasma cell neoplasms and the potential role of FcεRI(+)cMo in normal bone homeostasis. ABSTRACT: Background. Monocyte/macrophages have been shown to be altered in monoclonal gammopathy of undetermined significance (MGUS), smoldering (SMM) and active multiple myeloma (MM), with an impact on the disruption of the homeostasis of the normal bone marrow (BM) microenvironment. Methods: We investigated the distribution of different subsets of monocytes (Mo) in blood and BM of newly-diagnosed untreated MGUS (n = 23), SMM (n = 14) and MM (n = 99) patients vs. healthy donors (HD; n = 107), in parallel to a large panel of cytokines and bone-associated serum biomarkers. Results: Our results showed normal production of monocyte precursors and classical Mo (cMo) in MGUS, while decreased in SMM and MM (p ≤ 0.02), in association with lower blood counts of recently-produced CD62L(+) cMo in SMM (p = 0.004) and of all subsets of (CD62L(+), CD62L(−) and FcεRI(+)) cMo in MM (p ≤ 0.02). In contrast, intermediate and end-stage non-classical Mo were increased in BM of MGUS (p ≤ 0.03), SMM (p ≤ 0.03) and MM (p ≤ 0.002), while normal (MGUS and SMM) or decreased (MM; p = 0.01) in blood. In parallel, increased serum levels of interleukin (IL)1β were observed in MGUS (p = 0.007) and SMM (p = 0.01), higher concentrations of serum IL8 were found in SMM (p = 0.01) and MM (p = 0.002), and higher serum IL6 (p = 0.002), RANKL (p = 0.01) and bone alkaline phosphatase (BALP) levels (p = 0.01) with decreased counts of FcεRI(+) cMo, were restricted to MM presenting with osteolytic lesions. This translated into three distinct immune/bone profiles: (1) normal (typical of HD and most MGUS cases); (2) senescent-like (increased IL1β and/or IL8, found in a minority of MGUS, most SMM and few MM cases with no bone lesions); and (3) pro-inflammatory-high serum IL6, RANKL and BALP with significantly (p = 0.01) decreased blood counts of immunomodulatory FcεRI(+) cMo-, typical of MM presenting with bone lesions. Conclusions: These results provide new insight into the pathogenesis of plasma cell neoplasms and the potential role of FcεRI(+) cMo in normal bone homeostasis. MDPI 2021-03-22 /pmc/articles/PMC8004952/ /pubmed/33810169 http://dx.doi.org/10.3390/cancers13061454 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Damasceno, Daniela
Almeida, Julia
Teodosio, Cristina
Sanoja-Flores, Luzalba
Mayado, Andrea
Pérez-Pons, Alba
Puig, Noemi
Arana, Paula
Paiva, Bruno
Solano, Fernando
Romero, Alfonso
Matarraz, Sergio
van den Bossche, Wouter B. L.
Flores-Montero, Juan
Durie, Brian
van Dongen, Jacques J. M.
Orfao, Alberto
Monocyte Subsets and Serum Inflammatory and Bone-Associated Markers in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma
title Monocyte Subsets and Serum Inflammatory and Bone-Associated Markers in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma
title_full Monocyte Subsets and Serum Inflammatory and Bone-Associated Markers in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma
title_fullStr Monocyte Subsets and Serum Inflammatory and Bone-Associated Markers in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma
title_full_unstemmed Monocyte Subsets and Serum Inflammatory and Bone-Associated Markers in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma
title_short Monocyte Subsets and Serum Inflammatory and Bone-Associated Markers in Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma
title_sort monocyte subsets and serum inflammatory and bone-associated markers in monoclonal gammopathy of undetermined significance and multiple myeloma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004952/
https://www.ncbi.nlm.nih.gov/pubmed/33810169
http://dx.doi.org/10.3390/cancers13061454
work_keys_str_mv AT damascenodaniela monocytesubsetsandseruminflammatoryandboneassociatedmarkersinmonoclonalgammopathyofundeterminedsignificanceandmultiplemyeloma
AT almeidajulia monocytesubsetsandseruminflammatoryandboneassociatedmarkersinmonoclonalgammopathyofundeterminedsignificanceandmultiplemyeloma
AT teodosiocristina monocytesubsetsandseruminflammatoryandboneassociatedmarkersinmonoclonalgammopathyofundeterminedsignificanceandmultiplemyeloma
AT sanojafloresluzalba monocytesubsetsandseruminflammatoryandboneassociatedmarkersinmonoclonalgammopathyofundeterminedsignificanceandmultiplemyeloma
AT mayadoandrea monocytesubsetsandseruminflammatoryandboneassociatedmarkersinmonoclonalgammopathyofundeterminedsignificanceandmultiplemyeloma
AT perezponsalba monocytesubsetsandseruminflammatoryandboneassociatedmarkersinmonoclonalgammopathyofundeterminedsignificanceandmultiplemyeloma
AT puignoemi monocytesubsetsandseruminflammatoryandboneassociatedmarkersinmonoclonalgammopathyofundeterminedsignificanceandmultiplemyeloma
AT aranapaula monocytesubsetsandseruminflammatoryandboneassociatedmarkersinmonoclonalgammopathyofundeterminedsignificanceandmultiplemyeloma
AT paivabruno monocytesubsetsandseruminflammatoryandboneassociatedmarkersinmonoclonalgammopathyofundeterminedsignificanceandmultiplemyeloma
AT solanofernando monocytesubsetsandseruminflammatoryandboneassociatedmarkersinmonoclonalgammopathyofundeterminedsignificanceandmultiplemyeloma
AT romeroalfonso monocytesubsetsandseruminflammatoryandboneassociatedmarkersinmonoclonalgammopathyofundeterminedsignificanceandmultiplemyeloma
AT matarrazsergio monocytesubsetsandseruminflammatoryandboneassociatedmarkersinmonoclonalgammopathyofundeterminedsignificanceandmultiplemyeloma
AT vandenbosschewouterbl monocytesubsetsandseruminflammatoryandboneassociatedmarkersinmonoclonalgammopathyofundeterminedsignificanceandmultiplemyeloma
AT floresmonterojuan monocytesubsetsandseruminflammatoryandboneassociatedmarkersinmonoclonalgammopathyofundeterminedsignificanceandmultiplemyeloma
AT duriebrian monocytesubsetsandseruminflammatoryandboneassociatedmarkersinmonoclonalgammopathyofundeterminedsignificanceandmultiplemyeloma
AT vandongenjacquesjm monocytesubsetsandseruminflammatoryandboneassociatedmarkersinmonoclonalgammopathyofundeterminedsignificanceandmultiplemyeloma
AT orfaoalberto monocytesubsetsandseruminflammatoryandboneassociatedmarkersinmonoclonalgammopathyofundeterminedsignificanceandmultiplemyeloma