Lineage-related polypeptide markers in acute lymphoblastic leukemia detected by two-dimensional gel electrophoresis.

Hanash, Samir M.; Baier, Leslie J.; McCurry, Lynette; Schwartz, Stanley A.

doi:10.1073/pnas.83.3.807

Cited by 43 publications

(13 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Two polypeptides were noted to be highly abundant in the normal oesophagus and consistent with Hsp27 phosphoisoforms we previously identified by 2D-PAGE and sequenced (Hanash et al, 1986(Hanash et al, , 1988Strahler et al, 1990). We observed that Hsp27 is abundantly expressed in the normal oesophageal mucosa and exhibits a pattern of protein expression that corresponds with the degree of squamous cell maturation.…”

supporting

confidence: 53%

Differential expression of Hsp27 in normal oesophagus, Barrett’s metaplasia and oesophageal adenocarcinomas

et al. 1999

Self Cite

View full text Add to dashboard Cite

SummaryThe protein expression patterns of normal, metaplastic and malignant oesophageal tissues were analysed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) to identify changes associated with Barrett's metaplasia and transformation to oesophageal adenocarcinoma. Heat-shock protein 27 (Hsp27), a small heat-shock protein which is protective against cytotoxic stresses, was abundant in normal oesophagus. However, Hsp27 expression was markedly lower in Barrett's metaplasia and oesophageal adenocarcinomas. This was confirmed by immunohistochemical analysis. Hsp27 protein was most highly expressed in the upper layers of squamous epithelium and exhibited a pattern of expression that corresponded with the degree of squamous maturation. Northern and Southern analysis demonstrated Hsp27 to be regulated at the level of mRNA transcription or abundance. Normal oesophageal tissues were examined for gender differences in Hsp27 expression. Women expressed fourfold higher levels of Hsp27 mRNA, however, this difference was not appreciable in protein expression. Hsp27 protein was inducible by heat shock in Barrett's adenocarcinoma cell lines and an immortalized oesophageal epithelial cell line (HET-1A), but not by oestradiol. These results demonstrate abundant constitutive expression of the stress-response protein Hsp27 in the normal oesophagus, and suggest that low-level expression in Barrett's metaplasia may be one factor which may influence susceptibility to oesophageal adenocarcinoma development.

show abstract

supporting

confidence: 53%

Differential expression of Hsp27 in normal oesophagus, Barrett’s metaplasia and oesophageal adenocarcinomas

et al. 1999

Self Cite

View full text Add to dashboard Cite

show abstract

“…Cells to be studied by 2-dimensional polyacrylamide gel electrophoresis (2-D PAGE) were thoroughly washed to remove serum proteins, then used immediately or radioiodinated with I2'I using the lactoperoxidase technique (26). First and second dimensions were run as described (27), and spots analyzed for position and intensity on a Masscomp image analyzer computer system (BioImage, Ann Arbor, MI) using a 1,024 x 1,024-pixel format (160 plpixel) (28). To detect radioiodinated polypeptides, the gels were dried and sealed in light-tight cassettes with x-ray film (XAR-5; Eastman-Kodak, Rochester, NY) and Cronex enhancing screens (DuPont, Wilmington, DE).…”

Section: Methodsmentioning

confidence: 99%

Phenotypic and functional similarities between 5‐azacytidine‐treated t cells and a t cell subset in patients with active systemic lupus erythematosus

Richardson

Strahler

Pivirotto

et al. 1992

Arthritis & Rheumatism

164

159

View full text Add to dashboard Cite

Objective. Antigen-specific CD4+ T cells treated with DNA methylation inhibitors become autoreactive, suggesting a novel mechanism for autoimmunity. To test whether this mechanism might be involved in systemic lupus erythematosus (SLE), phenotypic markers for the autoreactive cells were sought.Methods. Cloned normal T cells were treated with the DNA methylation inhibitor 5-azacytidine (5-azaC) and studied for altered gene expression. T cells from patients with active SLE were then studied for a similar change in gene expression, and cells expressing the marker were tested for autoreactivity.Results. 5-azaC-treated normal T cells had increased CDlla (leukocyte function-associated antigen la) expression relative to other membrane molecules. A T cell subset with similar CDlla expression was found in patients with active SLE. This subset contained cells that spontaneously lysed autologous macrophages, with a specificity similar to that of 5-azaC-treated cells. Conclusion. The model of 5-azaC-induced autoreactivity may have relevance to SLE.Antigen-specific CD4+ T cell clones respond to autologous macrophages (Mgi) without antigen, following treatment with DNA methylation inhibitors such as 5-azacytidine (5-azaC). The response is inhibited by monoclonal antibodies (MAb) against CD3 and class I1 major histocompatibility complex (MHC) determinants, and occurs with autologous but not allogeneic Mgi (1,2), suggesting that the cells are responding to autologous class I1 MHC determinants via a pathway involving the antigedMHC receptor. Similar concentrations of 5-azaC alter gene expression in a wide range of cell types, including T cells (3-3, and the autoreactivity may be caused by changes in the expression of as-yet-unidentified genes involved in T cell activation.5-azaC-induced autoreactivity may have relevance to autoimmunity. Recent experiments have shown that murine T cells can become autoreactive following 5-azaC treatment, responding to and, intriguingly, lysing, syngeneic Mgi. Adoptive transfer of murine 5-azaC-treated cells induces an immune complex glomerulonephritis and anti-DNA antibodies in nonirradiated syngeneic mice (6). These findings suggest a novel model for systemic lupus erythematosus (SLE), in which T cell DNA hypomethylation could alter expression of crucial genes, resulting in T cell autoreactivity, and the autoreactive T cells could then produce a lupus-like illness. Reports that lupusinducing drugs inhibit T cell DNA methylation and induce autoreactivity (7) support this concept. Moreover, recent evidence indicates that T cell DNA methylation is impaired in patients with active SLE (8).

show abstract

“…Among some 400 polypeptides that were analyzed, 12 polypeptide were detected that could distinguish between the major subgroups of ALL and between ALL and acute myelogenous leukemia (AML). 31 These included a new marker for common ALL and markers for cells of B and T lineages. Analysis of the 2-D patterns also allowed the tentative identification of T-cell lineage in some cases with an otherwise undifferentiated non-T-cell non-B-cell phenotype.…”

Section: Proteomic Profiling Of Acute Leukemiamentioning

confidence: 99%

“…Partial amino acid sequence analysis of Op18, facilitated our ability to clone the gene. 31,[38][39][40] Interestingly, in a recent DNA microarray-based study of leukemias, Op18 was identified as one of the discriminators between ALL and AML. It should be noted that whereas with RNA based analysis, Op18 generates one measure, namely that of the levels of its corresponding RNA, at the protein level there is the potential of analyzing separately the different post-translationally modified forms of Op18.…”

Section: High Level Expression Of Op18 In Acute Lymphoid Leukemiasmentioning

confidence: 99%

“…This is illustrated by our investigation of the different subtypes of acute lymphoid leukemias in the 1980s using proteomics. 31 We utilized 2-D PAGE to identify polypeptide differences due to lineage among lymphoblasts obtained directly from peripheral blood or bone marrow of children with acute lymphoblastoid leukemia (ALL). The specific objectives were (1) to identify polypeptides that were limited in their occurrence to only a subset of the patients with ALL; (2) to relate the presence of these polypeptides to immunologic and other previously established markers, and (3) to attempt to identify the cell of origin of CALLA-negative non-T-cell, non-B-cell ALL.…”

Section: Proteomic Profiling Of Acute Leukemiamentioning

confidence: 99%

See 1 more Smart Citation

Identification of novel targets for cancer therapy using expression proteomics

2002

View full text Add to dashboard Cite

Although most drugs target proteins, the proteome has remained largely untapped for the discovery of drug targets. The sequencing of the human genome has had a tremendous impact on proteomics and has provided a framework for protein identification. There is currently substantial interest in implementing proteomics platforms for drug target discovery. Although the field is still in the early stages, current proteomic tools include a variety of technologies that could be implemented for large-scale protein expression analysis of cells and tissues, leading to discovery of novel drug targets. Proteomics uniquely allows delineation of global changes in protein expression patterns resulting from transcriptional and post-transcriptional control, post-translational modifications and shifts in proteins between different cellular compartments. Some of the current technologies for proteome profiling and the application of proteomics to the analysis of leukemias by our group are reviewed. Leukemia (2002) 16, 478-485.

show abstract

Lineage-related polypeptide markers in acute lymphoblastic leukemia detected by two-dimensional gel electrophoresis.

Cited by 43 publications

References 29 publications

Differential expression of Hsp27 in normal oesophagus, Barrett’s metaplasia and oesophageal adenocarcinomas

Differential expression of Hsp27 in normal oesophagus, Barrett’s metaplasia and oesophageal adenocarcinomas

Phenotypic and functional similarities between 5‐azacytidine‐treated t cells and a t cell subset in patients with active systemic lupus erythematosus

Identification of novel targets for cancer therapy using expression proteomics

Contact Info

Product

Resources

About