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Simple Summary: It is known that both B cells and myeloblasts from acute myeloid leukemia (AML) express immunoglobulin (Ig). However, the difference between Ig from myeloblasts and B cells has not been explored; therefore, the function and significance of AML-Ig are not well known. Here, we performed 5′ RACE-related PCR coupled with PacBio sequencing to analyze the Ig repertoire of Chinese AML patients. Myeloblasts expressed all five classes of IgH, especially Igγ, with a high expression frequency. Compared with B-Ig in the same AML patient, AML-Ig showed different biased V(D)J usages and mutation patterns. More importantly, mutations of AML-Ig frequently occurred at the sites of post-translational modification. In summary, our results showed that AML-Ig had different sequence characteristics than those of B-Ig and that the unique V(D)J usages of AML-Ig may serve as a novel biomarker for personalized minimal/measurable residual disease monitoring and therapeutic targets in AML patients. It is common knowledge that immunoglobulin (Ig) is produced by B lymphocytes and mainly functions as an antibody. However, it has been shown recently that myeloblasts from acute myeloid leukemia (AML) could also express Ig and that AML-Ig played a role in leukemogenesis and AML progression. The difference between Ig from myeloblasts and B cells has not been explored. Studying the characteristics of the Ig repertoire in myeloblasts and B cells will be helpful to understand the function and significance of AML-Ig. We performed 5′ RACE-related PCR coupled with PacBio sequencing to analyze the Ig repertoire in myeloblasts and B cells from Chinese AML patients. Myeloblasts expressed all five classes of IgH, especially Igγ, with a high expression frequency. Compared with B-Ig in the same patient, AML-Ig showed different biased V(D)J usages and mutation patterns. In addition, the CDR3 length distribution of AML-Ig was significantly different from those of B-Ig. More importantly, mutations of AML-IgH, especially Igμ, Igα, and Igδ, were different from that of B-IgH in each AML patient, and the mutations frequently occurred at the sites of post-translational modification. AML-Ig has distinct characteristics of variable regions and mutations, which may have implications for disease monitoring and personalized therapy. [ABSTRACT FROM AUTHOR]

Traditionally, immunoglobulin (Ig) was believed to be produced by only B-lineage cells. However, increasing evidence has revealed a high level of Ig expression in cancer cells, and this Ig is named cancer-derived Ig. Further studies have shown that cancer-derived Ig shares identical basic structures with B cell-derived Ig but exhibits several distinct characteristics, including restricted variable region sequences and aberrant glycosylation. In contrast to B cell-derived Ig, which functions as an antibody in the humoral immune response, cancer-derived Ig exerts profound protumorigenic effects via multiple mechanisms, including promoting the malignant behaviors of cancer cells, mediating tumor immune escape, inducing inflammation, and activating the aggregation of platelets. Importantly, cancer-derived Ig shows promising potential for application as a diagnostic and therapeutic target in cancer patients. In this review, we summarize progress in the research area of cancer-derived Ig and discuss the perspectives of applying this novel target for the management of cancer patients. [ABSTRACT FROM AUTHOR]

Objectives: It has been believed that immunoglobulins can only be produced by B lymphocytes and plasma cells. We have previously reported that IgG can be expressed in myeloblasts from patients with acute myeloid leukemia (AML) and plays a role in the proliferation and apoptosis of leukemic cells. However, its clinical impact has not been assessed. Methods: We assessed the expression of different classes of immunoglobulin in peripheral blood and bone marrow samples from 132 AML patients and correlated the levels of expression with clinicopathologic and molecular genetic features, as well as clinical outcome. Results: We found that, in addition to IgG, all classes of immunoglobulin are expressed in myeloblasts, including IgG, IgM, IgA, IgD, IgE, Igκ, and Igλ. The levels of IgG expression (coupled with Igκ or Igλ) are higher than those of IgM, IgA, IgD, and IgE. Using receiver operating characteristic (ROC) curve analysis, we identified two distinct groups of AML patients with differential expression of immunoglobulin and different clinical outcomes. Conclusions: High levels of immunoglobulin expression are associated with monocytic differentiation, multilineage dysplasia, TET2 and KRAS mutations, and poor overall survival. Assessment of immunoglobulin may serve as a useful marker for prognostic stratification and target therapy. [ABSTRACT FROM AUTHOR]

Glioma is the most common and most invasive primary central nervous system tumour, and it is urgent to develop new specific therapeutic targets. Studies have confirmed that epithelial-derived tumour cells promote tumour cell proliferation and metastasis by secreting a large number of immunoglobulins (Igs), but the role of tumour-derived Igs in glioma has never been reported. The Gene Expression Profiling Interactive Analysis and Chinese Glioma Genome Atlas databases were used to analyse the Ig transcription and its correlation with the prognosis of patients with glioma. Immunohistochemistry and immunofluorescence were used to detect the protein expression of IgG and IgM in the glioma tissues of patients and glioma cell lines. When IgG was knocked down by small interfering RNA or knocked out by CRISPR-Cas9, the function of proliferation and migration of glioma cells were analysed by CCK-8, clone formation, wound healing, and transwell assays. Changes in proteins and their phosphorylation in signalling pathways were detected by western blotting. The nude mouse subcutaneous tumour-bearing model was established to analyse the effect of IgG in vivo. The transcriptional level of IgG was pretty high in glioma tissues and was positively correlated with high WHO grade, recurrence, and poor prognosis. The expression of IgG and IgM was found in tumour tissues and human glioma cell lines U87 and U251, and the main expression form was secreted. Decreased IgG inhibited the proliferation and migration of glioma cells. Knockout or knockdown of IgG downregulated the phosphorylation of the key molecules in the MAPK and PI3K/Akt pathway through the HGF/SF-Met or FAK/Src pathway. In vivo tumourigenesis mouse model confirmed that reduced IgG expression inhibited glioma growth. Ig was expressed in glioma tissues and cell lines, and a high expression level predicted a poor prognosis of patients. Glioma-derived IgG promoted glioma cell proliferation and migration through the HGF/SF-Met or FAK/Src pathway. • Both glioma tissues and cell lines expressed immunoglobulin. • Glioma-derived IgG promoted proliferation and migration of glioma cells. • Reduction of IgG expression inhibited the growth of gliomas in mice. • Glioma-derived IgG may be a potential new target for glioma immunotherapy. [ABSTRACT FROM AUTHOR]

B cells and immunoglobulins are implicated in the pathogenesis of chronic diseases, including coronary artery disease (CAD). However, it remains elusive how the humoral immunity is incriminated in the disease progression of CAD. Using serum samples of chronic coronary syndrome (CCS) and acute myocardial infarction (AMI), we conducted a quantitative profiling of the proteomic landscape recognized by immunoglobulins, which we term immunoglobulin-associated proteome (IgAP). Intriguingly, CCS and AMI patients displayed distinctive IgAP profiles that enriched proteins in the pathways of blood coagulation regulation and lipoprotein transport, suggesting that CCS-AMI transition involves changes of these pathways that are associated with immunoglobulins. Furthermore, we identified immunoglobulin-bound coagulation factor X (F10) as a potential biomarker and validated it with an independent cohort of CCS, AMI and healthy individuals. Our study indicates that IgAP proteins may serve as novel diagnostic biomarkers for CCS and AMI. Our work it demonstrates a clear implication of immunoglobulin-associated proteome (IgAP), the proteomic landscape recognized by immunoglobulins, in the pathogenesis of CAD. In addition, it reports for the first time that immunoglobulin-bound F10 is implicated in CAD. [Display omitted] • Analysis of immunoglobulin-associated proteome (IgAP) using 20 μL of serum samples • Distinct IgAP between acute Myocardial Infarction (AMI) and Chronic Coronary Syndromes (CCS) patients • Enrichment of blood coagulation regulation and lipoprotein transport processes with differential AMI-CCS IgAP proteins • A progressive increase of immunoglobulin-bound coagulation factor X (F10) in healthy, CCS and AMI individuals [ABSTRACT FROM AUTHOR]