Immunoglobulin Expression in Cancer Cells and Its Critical Roles in Tumorigenesis

Cui, Ming; Huang, Jing; Zhang, Shenghua; Liu, Qiaofei; Liao, Quan; Qiu, Xiaoyan

doi:10.3389/fimmu.2021.613530

Cited by 49 publications

(52 citation statements)

References 106 publications

(120 reference statements)

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“…This study is the first to demonstrate that all the five classes of Ig heavy chains and two types of Ig light chains could be expressed in non-B cells. IGHG has been reported in various non-B neoplastic cells and has been shown to promote malignant behaviors in cancer cells [ 8 ]. Similarly, we detected a high frequency of IGHG expression in myeloblasts.…”

Section: Discussionmentioning

confidence: 99%

“…Monoclonal immunoglobulin (Ig) gene rearrangement has been used as a diagnostic tool for B-cell lymphomas [ 7 ]. Although B-cells and plasma cells have been considered as the only source of Ig, a series of reports from our group and others have demonstrated that Ig could be expressed in many epithelial cancer cells [ 8 ], as well as in normal non-hematopoietic cells [ 9 , 10 , 11 ]. Moreover, other than acting as natural antibodies [ 12 , 13 ], non-B-derived Ig, especially IgG, with unique rearrangement patterns or glycosylation profile, has been shown to play a role in promoting cancer cell survival and proliferation, as well as cancer invasion and metastasis [ 8 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Although B-cells and plasma cells have been considered as the only source of Ig, a series of reports from our group and others have demonstrated that Ig could be expressed in many epithelial cancer cells [ 8 ], as well as in normal non-hematopoietic cells [ 9 , 10 , 11 ]. Moreover, other than acting as natural antibodies [ 12 , 13 ], non-B-derived Ig, especially IgG, with unique rearrangement patterns or glycosylation profile, has been shown to play a role in promoting cancer cell survival and proliferation, as well as cancer invasion and metastasis [ 8 , 14 ]. Non-B-derived Ig was frequently expressed in hematopoietic cells, including umbilical cord CD34 + stem/progenitor cells (IgM) [ 15 ], AML blasts (IgG, IgM, and Igκ) [ 16 , 17 , 18 ], and mature myeloid cells (IgM, and Igκ) [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Next-Generation Sequencing Revealed a Distinct Immunoglobulin Repertoire with Specific Mutation Hotspots in Acute Myeloid Leukemia

Xia

Sun

et al. 2022

Biology

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Immunoglobulin (Ig) is known as a hallmark of B-lymphocytes exerting antibody functions. However, our previous studies demonstrated that myeloblasts from acute myeloid leukemia (AML) patients could also express Ig with distinct roles. Here, we quantified Ig (IGHG and IGK) transcripts by real-time PCR and performed a comprehensive analysis of Ig repertoire (both heavy chains and light chains) in AML blasts. We found that Ig was frequently expressed by AML blasts. A higher level of AML-derived IGHG expression correlated with a significantly shorter disease-free survival. Next-generation sequencing revealed dysregulated transcripts of all five Ig classes (IGHA, IGHD, IGHE, IGHG, and IGHM) and two Ig types (IGK and IGL) in AML. VH-D-JH rearrangements in myeloblasts were biased with individual specificity rather than generally diverse as in B-cells. Compared to AML-derived IgH, AML-derived IGK was more conserved among different AML samples. The frequently shared Vκ-Jκ patterns were IGKV3-20*01/IGKJ1*01, IGKV2D-28*01/IGKJ1*01, and IGKV4-1*01/IGKJ1*01. Moreover, AML-derived IGK was different from classical IGK in B-cells for the high mutation rates and special mutation hotspots at serine codons. Findings of the distinct Ig repertoire in myeloblasts may facilitate the discovery of a new molecular marker for disease monitoring and target therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Next-Generation Sequencing Revealed a Distinct Immunoglobulin Repertoire with Specific Mutation Hotspots in Acute Myeloid Leukemia

Xia

Sun

et al. 2022

Biology

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“…Importantly, cancer-derived immunoglobulins show potential applications as diagnostic and therapeutic targets for cancer patients. 31 Studies have shown that AML-derived IgG may be related to the occurrence of leukaemia and the progression of AML.…”

Section: Discussionmentioning

confidence: 99%

Development of a Prognostic Nomogram for Acute Myeloid Leukemia on IGHD Gene Family

Qiu¹,

Zhang²,

Zhang³

et al. 2021

IJGM

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Purpose Acute myeloid leukaemia (AML) is a common haematological disease in adults. The overall survival (OS) remains unsatisfactory. It is critical to identify potential prognostic biomarkers and develop a nomogram that predicts overall survival in patients with AML. Patients and Methods We used gene expression dataset and clinical data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) to identify differential expression analysis, survival analysis, and prognostic value of IGHD gene family ( IGHDs ) in AML patients. A risk score model was built through Lasso analysis and multivariate Cox regression. We also developed a nomogram and evaluated its accuracy with Harrell’s Harmony Index (C-index) and calibration curve. Last, the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database was used for external validation. Results IGHD1-20 mRNA expression level was an independent prognostic factor for patients with AML by multivariate analysis. After Lasso analysis and multivariate Cox regression, we constructed a 3-gene model ( IGHD1-1, IGHD1-20, IGHD3-16 ) associated with OS in AML. Risk score and age were validated as independent risk factors for prognosis and were used to build a nomogram. The C index and calibration curve results show that its ability to predict 1-year, 3-year and 5-year overall survival is accurate. Conclusion The mRNA level of IGHDs was increased in AML patients. IGHD1-20 was an independent risk factor for OS in AML patients. The IGHDs risk model ( IGHD1-1, IGHD1-20, IGHD3-16 ) relates to the OS of AML patients. The nomogram, including risk score and age, can conveniently and effectively predict the overall survival rate of patients.

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“…While germline IGH genotypes have generally been overlooked in GWAS and other disease association studies, partially due to genotyping challenges, there is increasing interest in investigating the effect of IGH germline genetic variation on the adaptive immune system and disease[3, 5]. In fact IGHV germline genetic variation has recently been associated with clinical phenotypes including infectious disease and vaccine response [11, 12, 13, 14], autoimmune/inflammatory conditions[15, 16, 17], and cancer[18].…”

Section: Introductionmentioning

confidence: 99%

ImmunoTyper-SR: A Novel Computational Approach for Genotyping Immunoglobulin Heavy Chain Variable Genes using Short Read Data

Ford¹,

Hari²,

Rodriguez³

et al. 2022

Preprint

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Human immunoglobulin heavy chain (IGH) locus on chromosome 14 includes more than 40 functional copies of the variable gene (IGHV), which, together with the joining genes (IGHJ), diversity genes (IGHD), constant genes (IGHC) and immunoglobulin light chains, code for antibodies that identify and neutralize pathogenic invaders as a part of the adaptive immune system. Because of its highly repetitive sequence composition, the IGH locus has been particularly difficult to assemble or genotype through the use of standard short read sequencing technologies. Here we introduce ImmunoTyper-SR, an algorithmic method for genotype and CNV analysis of the germline IGHV genes using Illumina whole genome sequencing (WGS) data. ImmunoTyper-SR is based on a novel combinatorial optimization formulation that aims to minimize the total edit distance between reads and their assigned IGHV alleles from a given database, with constraints on the number and distribution of reads across each called allele. We have validated ImmunoTyper-SR on 12 individuals with Illumina WGS data from the 1000 Genomes Project, whose IGHV allele composition have been studied extensively through the use of long read and targeted sequencing platforms, as well as nine individuals from the NIAID COVID Consortium who have been subjected to WGS twice. We have then applied ImmunoTyper-SR on 585 samples from the NIAID COVID Consortium to investigate associations between distinct IGHV alleles and anti-type I IFN autoantibodies which have been linked to COVID-19 severity.

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Immunoglobulin Expression in Cancer Cells and Its Critical Roles in Tumorigenesis

Cited by 49 publications

References 106 publications

Next-Generation Sequencing Revealed a Distinct Immunoglobulin Repertoire with Specific Mutation Hotspots in Acute Myeloid Leukemia

Next-Generation Sequencing Revealed a Distinct Immunoglobulin Repertoire with Specific Mutation Hotspots in Acute Myeloid Leukemia

Development of a Prognostic Nomogram for Acute Myeloid Leukemia on IGHD Gene Family

ImmunoTyper-SR: A Novel Computational Approach for Genotyping Immunoglobulin Heavy Chain Variable Genes using Short Read Data

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