Surface localization of high-mobility group nucleosome-binding protein 2 on leukemic B cells from patients with chronic lymphocytic leukemia is related to secondary autoimmune hemolytic anemia

Pe, Morande; Borge, Mercedes; Abreu, Cecilia; Galletti, Jeremías Gastón; Zanetti, Marcelo Serrano; Nannini, Paula Romina; Rf, Bezares; Pantano, Sergio; Dighiero, G; Oppezzo, Pablo; Gamberale, Romina; Giordano, Mirta

doi:10.3109/10428194.2014.957205

Cited by 5 publications

(4 citation statements)

References 27 publications

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“…Likewise, the levels of HMGN1 in the serum of NSCLC individuals were higher in non-metastatic stages (I-III) as compared to the metastatic stage (IV), suggesting that HMGN1 can serve as a biomarker for early stages of NSCLC [49]. Leukemic B cells from patients with chronic lymphoblastic leukemia express HMGN2 on their surface; the HMGN2 variant acts as an autoantigen and contributes to the development of autoimmune hemolytic anemia [50]. Individuals with Down syndrome have a significantly increased risk of developing B cell acute lymphoblastic leukemia (B-ALL).…”

Section: Cancermentioning

confidence: 99%

Biological Functions of HMGN Chromosomal Proteins

Nanduri

Furusawa

Bustin

2020

IJMS

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Chromatin plays a key role in regulating gene expression programs necessary for the orderly progress of development and for preventing changes in cell identity that can lead to disease. The high mobility group N (HMGN) is a family of nucleosome binding proteins that preferentially binds to chromatin regulatory sites including enhancers and promoters. HMGN proteins are ubiquitously expressed in all vertebrate cells potentially affecting chromatin function and epigenetic regulation in multiple cell types. Here, we review studies aimed at elucidating the biological function of HMGN proteins, focusing on their possible role in vertebrate development and the etiology of disease. The data indicate that changes in HMGN levels lead to cell type-specific phenotypes, suggesting that HMGN optimize epigenetic processes necessary for maintaining cell identity and for proper execution of specific cellular functions. This manuscript contains tables that can be used as a comprehensive resource for all the English written manuscripts describing research aimed at elucidating the biological function of the HMGN protein family.

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Section: Cancermentioning

confidence: 99%

Biological Functions of HMGN Chromosomal Proteins

Nanduri

Furusawa

Bustin

2020

IJMS

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“…These include non‐histone chromosomal protein HMGN2 (+6·3‐fold) and CLTA (+4·9‐fold), which were both found at higher levels in B‐CLL cells compared to healthy controls (Fig B, D). HMGN2 is involved in the initiation of autoimmune haemolytic anaemia secondary to CLL (Morande et al , ) and B‐cell receptor (BCR) stimulation results in a strong increase in CXCR3 membrane expression mainly through CLTA‐mediated receptor internalization (Vlad et al , ). Conversely, immunoglobulin kappa constant (−5·2‐fold), MIF (−5·8‐fold) and PNP (−6·5‐fold), were found at lower levels in CLL cells compared to normal B cells (Fig C).…”

Section: Resultsmentioning

confidence: 99%

Altered expression of metabolic pathways in CLL detected by unlabelled quantitative mass spectrometry analysis

et al. 2019

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Summary Chronic lymphocytic leukaemia (CLL) remains the most common incurable malignancy of B cells in the western world. Patient outcomes are heterogeneous and can be difficult to predict with current prognostic markers. Here, we used a quantitative label‐free proteomic technique to ascertain differences in the B‐cell proteome from healthy donors and CLL patients with either mutated (M‐CLL) or unmutated (UM‐CLL) IGHV to identify new prognostic markers. In peripheral B‐CLL cells, 349 (22%) proteins were differentially expressed between normal B cells and B‐CLL cells and 189 (12%) were differentially expressed between M‐CLL and UM‐CLL. We also examined the proteome of proliferating CLL cells in the lymph nodes, and identified 76 (~8%) differentially expressed proteins between healthy and CLL lymph nodes. B‐CLL cells show over‐expression of proteins involved in lipid and cholesterol metabolism. A comprehensive lipidomic analysis highlighted large differences in glycolipids and sphingolipids. A shift was observed from the pro‐apoptotic lipid ceramide towards the anti‐apoptotic/chemoresistant lipid, glucosylceramide, which was more evident in patients with aggressive disease (UM‐CLL). This study details a novel quantitative proteomic technique applied for the first time to primary patient samples in CLL and highlights that primary CLL lymphocytes display markers of a metabolic shift towards lipid synthesis and breakdown.

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“…Moreover, increased HMGN2 expression is associated with the development of cancer and autoimmune diseases (Bustin, Reisch, Einck, & Klippel, 1982; Okamura et al, 1999). HMGN2 is also highly expressed in many cancer cell lines, including leukemia (Morande et al., 2015), breast cancer (Medler et al., 2016), osteosarcoma (Liang et al., 2015), OSCC (Li et al., 2018), and tongue carcinoma (Liu et al., 2014). Its increased expression was also observed in human OSCC tissues, particularly in metastatic OSCC tissues when compared with normal oral tissues (Li et al., 2018).…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic analysis of peripheral blood mononuclear cells in head and neck squamous cell carcinoma patients

et al. 2020

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Objectives To investigate the gene expression profile of peripheral blood mononuclear cells (PBMCs) from head and neck squamous cell carcinoma (HNSCC), including oral cancer (OC) and oropharyngeal cancer (OPC) patients, and compare them with healthy controls (HC). Materials and Methods Transcriptomic analysis of PBMCs was performed by RNA‐sequencing. The upregulated candidate genes were selected for validation by quantitative real‐time polymerase chain reaction (qPCR). In addition, related plasma protein levels were determined by enzyme‐linked immunosorbent assay (ELISA). Results Three significantly upregulated genes, including high mobility group nucleosomal binding domain 2 (HMGN2), folate receptor gamma (FOLR3), and amphiregulin (AREG), were selected. In the first cohort, the results showed that only HMGN2 expression was significantly increased in OC patients. In the larger sample size, the overall results demonstrated that HMGN2 expression had a tendency to increase in both OC and OPC patients compared with HC. Interestingly, the plasma HMGN2 (HMG‐17) protein level exhibited the same trend as that observed at the transcriptional level. Conclusion HMGN2 expression and plasma HMG‐17 (HMGN2 protein) were increased in both cancer patients compared with HC. This gene may be important for further functional studies in the PBMCs of HNSCC patients.

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Surface localization of high-mobility group nucleosome-binding protein 2 on leukemic B cells from patients with chronic lymphocytic leukemia is related to secondary autoimmune hemolytic anemia

Cited by 5 publications

References 27 publications

Biological Functions of HMGN Chromosomal Proteins

Biological Functions of HMGN Chromosomal Proteins

Altered expression of metabolic pathways in CLL detected by unlabelled quantitative mass spectrometry analysis

Transcriptomic analysis of peripheral blood mononuclear cells in head and neck squamous cell carcinoma patients

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