The SLAMF3 rs509749 polymorphism correlates with malignant potential in multiple myeloma

Ishibashi, Mariko; Sunakawa-Kii, Mika; Kaito, Yuta; Kinoshita, Ryosuke; Asayama, Toshio; Kuribayashi, Yasuko; Inokuchi, Koiti; Morita, Rimpei; Tamura, Hideto

doi:10.1016/j.exphem.2020.08.006

Cited by 7 publications

(7 citation statements)

References 30 publications

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“…We studied 68 Japanese patients with MM to determine the rs509749 allelic frequency in this population. The G allele was dominant (G = 0.76), and the frequencies of the GG, GA, and AA genotypes were 61.8%, 29.4%, and 8.8%, respectively, which were very similar to those in healthy Japanese controls [ 69 ]. Interestingly, MM patients harboring the rs509749 GG genotype had significantly shorter overall survival durations than those harboring the GA and AA genotypes ( p = 0.046).…”

Section: Slamf3 (Cd229 Ly9)mentioning

confidence: 86%

“…Interestingly, MM patients harboring the rs509749 GG genotype had significantly shorter overall survival durations than those harboring the GA and AA genotypes ( p = 0.046). We further determined that in MM cells, the A allele of rs509749 was associated with a markedly lower SLAMF3 binding affinity for SHP2 and GRB2 when compared with the G allele, and this reduced affinity led to decreases in ERK activation and aggressive MM behaviors [ 69 ]. Therefore, the G allele of the SLAMF3 SNP rs509749 might be a risk factor for MM development but not for plasma cell tumorigenesis.…”

Section: Slamf3 (Cd229 Ly9)mentioning

confidence: 99%

“…Although many reports have described NK-cell activation mediated via EAT-2-induced signals through the SLAMF7–SLAMF7 interaction, the adaptor protein-mediated signaling pathway downstream of SLAMF7 in MM cells remains unclear due to the deficiencies of both SAP and EAT-2 in these cells [ 69 , 78 ]. In EAT-2-deficient NK cells, SLAMF7 triggers tyrosine phosphorylation of SHIP-1 via CD45-dependent activation of Src kinases, inhibiting NK-cell function [ 93 ].…”

Section: Slamf7 (Cd319 Cs1)mentioning

confidence: 99%

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Immune Functions of Signaling Lymphocytic Activation Molecule Family Molecules in Multiple Myeloma

Ishibashi

Morita

Tamura

2021

Cancers

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The signaling lymphocytic activation molecule (SLAM) family receptors are expressed on various immune cells and malignant plasma cells in multiple myeloma (MM) patients. In immune cells, most SLAM family molecules bind to themselves to transmit co-stimulatory signals through the recruiting adaptor proteins SLAM-associated protein (SAP) or Ewing’s sarcoma-associated transcript 2 (EAT-2), which target immunoreceptor tyrosine-based switch motifs in the cytoplasmic regions of the receptors. Notably, SLAMF2, SLAMF3, SLAMF6, and SLAMF7 are strongly and constitutively expressed on MM cells that do not express the adaptor proteins SAP and EAT-2. This review summarizes recent studies on the expression and biological functions of SLAM family receptors during the malignant progression of MM and the resulting preclinical and clinical research involving four SLAM family receptors. A better understanding of the relationship between SLAM family receptors and MM disease progression may lead to the development of novel immunotherapies for relapse prevention.

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Section: Slamf3 (Cd229 Ly9)mentioning

confidence: 86%

Section: Slamf3 (Cd229 Ly9)mentioning

confidence: 99%

Section: Slamf7 (Cd319 Cs1)mentioning

confidence: 99%

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Immune Functions of Signaling Lymphocytic Activation Molecule Family Molecules in Multiple Myeloma

Ishibashi

Morita

Tamura

2021

Cancers

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“…Several other chromosomal translocations and mutations were further reported that can be utilized as biomarkers in MM. These genetic alterations were found to be associated with chemotherapy-induced peripheral neuropathy [ 118 ], correlating with the outcome and survival of MM patients [ 119 , 120 , 121 , 122 , 123 , 124 , 125 ] and indicating the clinical response to treatment [ 126 , 127 ].…”

Section: Novel Biomarkers For Diagnosis and Prognosis Of MMmentioning

confidence: 99%

Next-Generation Biomarkers in Multiple Myeloma: Understanding the Molecular Basis for Potential Use in Diagnosis and Prognosis

Soliman

Das

Teoh

2021

IJMS

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Multiple myeloma (MM) is considered to be the second most common blood malignancy and it is characterized by abnormal proliferation and an accumulation of malignant plasma cells in the bone marrow. Although the currently utilized markers in the diagnosis and assessment of MM are showing promising results, the incidence and mortality rate of the disease are still high. Therefore, exploring and developing better diagnostic or prognostic biomarkers have drawn global interest. In the present review, we highlight some of the recently reported and investigated novel biomarkers that have great potentials as diagnostic and/or prognostic tools in MM. These biomarkers include angiogenic markers, miRNAs as well as proteomic and immunological biomarkers. Moreover, we present some of the advanced methodologies that could be utilized in the early and competent diagnosis of MM. The present review also focuses on understanding the molecular concepts and pathways involved in these biomarkers in order to validate and efficiently utilize them. The present review may also help in identifying areas of improvement for better diagnosis and superior outcomes of MM.

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“…Other studies have con rmed that LY9 expression can inactivate E2F transcription factors, reducing PLK1 production and activation, thereby presenting anti-cancer effects in hepatocellular carcinoma [22]. Additionally, LY9 is widely expressed on plasma cells from individuals with multiple myeloma (MM) and can promote a high level of malignant potential in tumor cells through ERK signaling, regulated by the junctional proteins SHP2 and GRB2 [23]. LY9 can also act as a tumor-related antigen in chronic lymphocytic leukemia, and patients with high LY9 expression have a worse prognosis [24].…”

Section: Introductionmentioning

confidence: 99%

Lymphocyte Antigen 9 as a potential immunotherapeutic target and a new prognostic biomarker for lung adenocarcinoma

Deng

Yuan

et al. 2022

Preprint

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BackgroundLymphocyte Antigen 9 (LY9) participates in the development of several tumors and diseases. However, it has not been reported yet in lung adenocarcinoma (LUAD). MethodsFirst, we retrieved the pan-cancer transcriptomic and clinical data from the UCSC official website and performed LY9 differential expression analysis. Then, we used the Kaplan-Meier Plotter and GEPIA databases to perform prognostic analysis of LY9 expression in pan-cancer. Additionally, we conducted correlation analysis of LY9 expression in LUAD with immune cell infiltration using the TIMER database and the CIBERSOFT algorithm, and with immune checkpoints using the GEPIA database. Also, we constructed a potential ceRNA network for LY9. Furthermore, we explored LY9-related pathways by Gene Set Enrichment Analysis. Finally, we collected LUAD tissues for Quantitative Real-time PCR to verify the expression of LY9, CD8, and CD4 and calculated the correlation between them. ResultsResults showed that LY9 was highly expressed in various tumors, including LUAD. Besides, patients with high LY9 expression presented longer overall survival and more multiple lymphocyte infiltrations. The expression of LY9 in LUAD promotes the infiltration of multiple immune cells, while significantly and positively correlating with immune checkpoints. The functional enrichment analysis indicated that LY9 was involved in multiple immune-related pathways and non-small cell lung cancer. Moreover, a ceRNA regulatory network of LINC00943-hsa-miR-141-3p-LY9 might be involved. Finally, the qRT-PCR results verified that the expression of LY9 in LUAD has a strong and positive correlation with CD4 and CD8 T cells. ConclusionSo LY9 can be a new prognostic biomarker and immunotherapeutic target for LUAD.

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The SLAMF3 rs509749 polymorphism correlates with malignant potential in multiple myeloma

Cited by 7 publications

References 30 publications

Immune Functions of Signaling Lymphocytic Activation Molecule Family Molecules in Multiple Myeloma

Immune Functions of Signaling Lymphocytic Activation Molecule Family Molecules in Multiple Myeloma

Next-Generation Biomarkers in Multiple Myeloma: Understanding the Molecular Basis for Potential Use in Diagnosis and Prognosis

Lymphocyte Antigen 9 as a potential immunotherapeutic target and a new prognostic biomarker for lung adenocarcinoma

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