Altered cytokine and chemokine profiles in multiple myeloma and its precursor disease

Zingone, Adriana; Wang, Weixin; Corrigan-Cummins, Meghan; Plyler, Ryan J.; Korde, Neha; Kwok, Mary; Manasanch, Elisabet E.; Tageja, Nishant; Bhutani, Manisha; Mulquin, Marcia; Zuchlinski, Diamond; Yancey, Mary Ann; Roschewski, Mark; Zhang, Yong; Roccaro, Aldo M.; Ghobrial, Irène M.; Calvo, Katherine R.; Landgren, Ola

doi:10.1016/j.cyto.2014.05.017

“…Elevated levels of several chemokines have previously been documented in MM and are thought to play a role in promoting MM proliferation and survival [27–29, 31, 32, 34, 36, 39, 40]. The source of these chemokines appears to derive from both the myeloma plasma cells and associated stromal cells [34, 36, 40, 41].…”

Section: Discussionmentioning

confidence: 99%

Neoplastic plasma cells generate an inflammatory environment within bone marrow and markedly alter the distribution of T cells between lymphoid compartments

Goodyear

¹

,

Essex

²

,

Anandram

³

et al. 2017

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Monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) are characterised by the accumulation of malignant plasma cells within bone marrow and lead to a range of abnormalities in the peripheral blood T cell repertoire. We investigated the level of inflammatory chemokines within the bone marrow and blood of patients with MGUS and MM and related this to the pattern of chemokine receptor expression on T cells in both compartments.The expression of a wide range of chemokine ligands for CXCR3 and CCR4 was markedly increased within the bone marrow of patients with MGUS and MM compared to healthy donors. The most marked effects were seen for CCL4 and CXCL9 which were increased by 4 and 6 fold respectively in the bone marrow of patients with myeloma. The expression of CXCR3 and CCR4, the major TH1 and TH2-associated chemokine receptors, was increased substantially on T cells within the bone marrow of patients whereas the percentage of CXCR3-expressing T cells within blood was correspondingly decreased. The presence of even small numbers of neoplastic plasma cells or associated stroma can therefore generate an inflammatory chemokine tumour microenvironment. This leads to the selective recruitment or retention of specific T cell subsets which is likely to underlie many of the features regarding the peripheral T cell repertoire in myeloma and may also contribute to the immune suppression associated with this disease. This local inflammatory reaction may represent a tumour-specific immune response or may itself play an important role in tumour progression and as such may offers a potential novel target for therapeutic intervention.

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“…As secreted proteins with functions in growth, differentiation, and activation, cytokines and chemokines play an important role in regulating the nature of immune responses. The contents of cytokines and chemokines in the peripheral blood and bone marrow supernatant of patients with MM were greatly increased compared to those in patients with SMM (Zingone et al, 2014). This finding might shed light on the decision to initiate chemotherapy and on disease status monitoring.…”

Section: Discussionmentioning

confidence: 84%

Pathway-based network analysis of myeloma tumors: monoclonal gammopathy of unknown significance, smoldering multiple myeloma, and multiple myeloma

Dong¹,

Chen²,

Xu³

et al. 2015

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ABSTRACT. Although many studies have been carried out on monoclonal gammopathy of unknown significances (MGUS), smoldering multiple myeloma (SMM), and multiple myeloma (MM), their classification and underlying pathogenesis are far from elucidated. To discover the relationships among MGUS, SMM, and MM at the transcriptome level, differentially expressed genes in MGUS, SMM, and MM were identified by the rank product method, and then coexpression networks were constructed by integrating the data. Finally, a pathway-network was constructed based on Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and the relationships between the pathways were identified. The results indicated that there were 55, 78, and 138 pathways involved in the myeloma tumor developmental stages of MGUS, SMM, and MM, respectively. The biological processes identified therein were found to have a close relationship with the immune system. Processes and pathways related to the abnormal activity of DNA and RNA were also present in SMM and MM. Six common pathways were found in the whole process of myeloma tumor development. Nine pathways were shown to participate in the progression of MGUS to SMM, and prostate cancer was the sole pathway that was involved only in MGUS and MM. Pathway-network analysis might provide a new indicator for the developmental stage diagnosis of myeloma tumors.

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“…Other chemokines have been shown to be elevated in patients with multiple myeloma including CCL3 and CCL20 [29][30]. Increased levels of key cytokines have also been shown to progressively increase from controls to smouldering myeloma to multiple myeloma including CXCL8 (IL-8), IL-10, TNFα, IL6 and IFNγ [31] . A decrease in NK cell numbers in the bone marrow of patients with myeloma has been shown to correlate with a decrease in the chemokine CXCL12 and an upregulation of CXCR3 ligand expression [32].…”

Section: Research Papermentioning

confidence: 99%

“…The expression of CXC chemokines such as CXCL12 (SDF-1) and CXCL8 (IL-8) has been reported to be modulated in patients with MM [31,[33][34][35][36]. CXCL12 is the ligand for CXCR4 whereas CXCL8 binds to the CXCR1 and CXCR2 receptors.…”

Section: The Expression Of a Wide Range Of Inflammatory Chemokines Ismentioning

confidence: 99%

Neoplastic Plasma Cells Generate an Inflammatory Environment Within Bone Marrow and Markedly Alter the Distribution of T Cells Between Lymphoid Compartments

Pratt

¹

,

Goodyear

²

,

Basu

³

et al. 2017

Clinical Lymphoma Myeloma and Leukemia

0

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Monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) are characterised by the accumulation of malignant plasma cells within bone marrow and lead to a range of abnormalities in the peripheral blood T cell repertoire. We investigated the level of inflammatory chemokines within the bone marrow and blood of patients with MGUS and MM and related this to the pattern of chemokine receptor expression on T cells in both compartments.The expression of a wide range of chemokine ligands for CXCR3 and CCR4 was markedly increased within the bone marrow of patients with MGUS and MM compared to healthy donors. The most marked effects were seen for CCL4 and CXCL9 which were increased by 4 and 6 fold respectively in the bone marrow of patients with myeloma. The expression of CXCR3 and CCR4, the major TH1 and TH2-associated chemokine receptors, was increased substantially on T cells within the bone marrow of patients whereas the percentage of CXCR3-expressing T cells within blood was correspondingly decreased. The presence of even small numbers of neoplastic plasma cells or associated stroma can therefore generate an inflammatory chemokine tumour microenvironment. This leads to the selective recruitment or retention of specific T cell subsets which is likely to underlie many of the features regarding the peripheral T cell repertoire in myeloma and may also contribute to the immune suppression associated with this disease. This local inflammatory reaction may represent a tumour-specific immune response or may itself play an important role in tumour progression and as such may offers a potential novel target for therapeutic intervention.

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Altered cytokine and chemokine profiles in multiple myeloma and its precursor disease

Cited by 16 publications

References 15 publications

Neoplastic plasma cells generate an inflammatory environment within bone marrow and markedly alter the distribution of T cells between lymphoid compartments

Neoplastic plasma cells generate an inflammatory environment within bone marrow and markedly alter the distribution of T cells between lymphoid compartments

Pathway-based network analysis of myeloma tumors: monoclonal gammopathy of unknown significance, smoldering multiple myeloma, and multiple myeloma

Neoplastic Plasma Cells Generate an Inflammatory Environment Within Bone Marrow and Markedly Alter the Distribution of T Cells Between Lymphoid Compartments

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