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Stromal alterations in patients with monoclonal gammopathy of undetermined significance, smoldering myeloma, and multiple myeloma.
Bogun, Lucienne; Koch, Annemarie; Scherer, Bo; Fenk, Roland; Maus, Uwe; Bormann, Felix; Köhrer, Karl; Petzsch, Patrick; Wachtmeister, Thorsten; Zukovs, Romans; Dietrich, Sascha; Haas, Rainer; Schroeder, Thomas; Jäger, Paul; Geyh, Stefanie.
Afiliação
  • Bogun L; Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Duesseldorf, Germany.
  • Koch A; Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Duesseldorf, Germany.
  • Scherer B; Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Duesseldorf, Germany.
  • Fenk R; Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Duesseldorf, Germany.
  • Maus U; Department of Orthopedic Surgery and Traumatology, University Hospital Duesseldorf, Medical Faculty, Duesseldorf, Germany.
  • Bormann F; Bioinformatics.Expert UG, Berlin, Germany.
  • Köhrer K; Biological and Medical Research Center, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany.
  • Petzsch P; Biological and Medical Research Center, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany.
  • Wachtmeister T; Biological and Medical Research Center, Medical Faculty, Heinrich-Heine-University, Duesseldorf, Germany.
  • Zukovs R; Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Duesseldorf, Germany.
  • Dietrich S; Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Duesseldorf, Germany.
  • Haas R; Institute of Medical Microbiology and Hospital Hygiene, University of Duesseldorf, Medical Faculty, Duesseldorf, Germany.
  • Schroeder T; Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Duesseldorf, Germany.
  • Jäger P; Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Duesseldorf, Germany.
  • Geyh S; Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Duesseldorf, Germany.
Blood Adv ; 8(10): 2575-2588, 2024 May 28.
Article em En | MEDLINE | ID: mdl-38241490
ABSTRACT
ABSTRACT The hallmark of multiple myeloma (MM) is a clonal plasma cell infiltration in the bone marrow accompanied by myelosuppression and osteolysis. Premalignant stages such as monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic stages such as smoldering myeloma (SMM) can progress to MM. Mesenchymal stromal cells (MSCs) are an integral component of the bone marrow microenvironment and play an important role in osteoblast differentiation and hematopoietic support. Although stromal alterations have been reported in MM contributing to hematopoietic insufficiency and osteolysis, it is not clear whether alterations in MSC already occur in MGUS or SMM. In this study, we analyzed MSCs from MGUS, SMM, and MM regarding their properties and functionality and performed messenger RNA sequencing to find underlying molecular signatures in different disease stages. A high number of senescent cells and a reduced osteogenic differentiation capacity and hematopoietic support were already present in MGUS MSC. As shown by RNA sequencing, there was a broad spectrum of differentially expressed genes including genes of the BMP/TGF-signaling pathway, detected already in MGUS and that clearly increases in patients with SMM and MM. Our data may help to block these signaling pathways in the future to hinder progression to MM.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Gamopatia Monoclonal de Significância Indeterminada / Células-Tronco Mesenquimais / Mieloma Múltiplo Latente / Mieloma Múltiplo Limite: Aged / Female / Humans / Male Idioma: En Revista: Blood Adv Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Alemanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Gamopatia Monoclonal de Significância Indeterminada / Células-Tronco Mesenquimais / Mieloma Múltiplo Latente / Mieloma Múltiplo Limite: Aged / Female / Humans / Male Idioma: En Revista: Blood Adv Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Alemanha