Fibromodulin is an extracellular matrix protein normally produced by collagen-rich tissues; the fibromodulin gene has been found to be the most overexpressed gene in B-cell chronic lymphocytic leukemia. In this study, fibromodulin was expressed at the gene level (
Type 1 diabetes is recognized as an autoimmune inflammatory disease and low grade inflammation is also observed in type 2 diabetic patients. Interleukin 17 (IL-17) is a new player in inflammation. Th17 cells, as the main source of IL-17, require transforming growth factor β (TGF-β) and interleukin 23 (IL-23). The aim of this study was to investigate serum IL-17, IL-23 and TGF-β levels in diabetic patients and controls. In this case-control study, serum levels of IL-17, IL-23, and TGF-β were measured in 24 type 1 diabetic patients and 30 healthy controls using the ELISA method. Simultaneously, the same methodology was used to compare serum concentration of these three cytokines in 38 type 2 diabetic patients and 40 healthy controls. There was no significant difference between serum levels of IL-17 and IL-23 cytokines between cases and controls. However, TGF-β was significantly lower in type 1 diabetic patients (P < 0.001). Serum IL-17 and IL-23 levels demonstrate no association with type 1 and type 2 diabetes, but, in line with previous studies, TGF-β levels were lower in type 1 diabetic patients.
Recent molecular investigations have demonstrated over-expression of a large number of tumor associated antigens (TAAs) in a variety of malignancies. Over-expression of ROR1 gene, a member of the receptor tyrosine kinase family, has recently been reported in B-cell chronic lymphocytic leukemia. Wilms' tumor gene 1 (WT1) has long been known as a universal TAA expressed in a variety of solid and hematopoietic malignancies. In the present study, the expression profile of ROR1 and WT1 was investigated in different immunophenotypic subsets of B-cell acute lymphoblastic leukemia (B-ALL) patients. RT-PCR method was used to determine the ROR1 and WT1 genes expression in bone marrow (BM) and peripheral blood (PB) samples from 51 newly diagnosed Iranian B-ALL patients. Isolated tumor cells from all patients were immunophenotyped by flow cytometry. Based on immunophenotypic results, our B-ALL patients were classified in four differentiation subsets; Pro-B (n = 7), Pre-B I (n = 29), Pre-B II (n = 13) and Immature/mature B-ALL (n = 2). Although ROR1 was over-expressed in more mature subsets (16.7%, 42.9%, 45.5% and 100%, respectively), WT1 was more represented in immature subsets of B-ALL patients (57.1%, 64.3%, 38.5% and 0%, respectively). Comparison of the frequency of ROR1 and WT1 positive samples at each immunophenotypic subtype revealed statistically significant difference only in Pre B I subtype (p = 0.02). Our results suggest that expression of ROR1 and WT1 in B-ALL is associated with the differentiation stage of the leukemic cells.
Receptor tyrosine kinases (RTKs) are a group of enzymes involved in a variety of physiological and pathological processes. The human Ror1 is a member of the RTK family with unknown ligand and biological function. Overexpression of Ror1 has recently been reported in B-cell chronic lymphocytic leukemia. The aim of this study was to explore the expression profile of Ror1 in acute lymphoblastic leukemia (ALL) cells. Therefore, leukemic cells were isolated from the bone marrow and/or peripheral blood (PB) of 57 ALL patients. Immunophenotyping was performed by flow cytometry and mRNA expression was detected by RT-PCR. Overexpression of Ror1 mRNA was detected in 23 of 57 (40%) ALL patients. A similar expression pattern was observed in ALL cell lines, with 4 of 12 (33%) being positive. Stimulation of normal PB mononuclear cells with pokeweed mitogen and phorbol myristate acetate induced substantially higher Ror1 mRNA expression compared to unstimulated cultured cells. There has been neither a significant association between Ror1 expression and the immunophenotypic profile of the leukemic cells, nor with other clinical or hematological features of the patients. In conclusion, our findings propose Ror1 as a new tumor-associated antigen and a potential tool for targeted immunotherapy and monitoring of minimal residual disease in ALL.
Galectin-1 (Gal-1) and galectin-3 (Gal-3) molecules are involved in many vital, biological, and pathological processes. In this study the expression pattern of these two molecules was investigated in leukemic cells from 85 Iranian chronic lymphocytic leukemia (CLL) patients, classified into indolent, progressive, mutated, and unmutated subtypes by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) and flow cytometry methods. Our results showed significant downregulation of Gal-3, but not Gal-1, in CLL patients compared with normal subjects (p < .001). Higher representation of Gal-3 mRNA was observed in indolent patients compared with the progressive group (p < .05). Our findings imply a regulatory role for Gal-3 gene in initiation and/or progression of CLL.
Human IgG is comprised of four subclasses (IgG(1), IgG(2), IgG(3), and IgG(4)). Each subclass possesses different biological properties. One of the differential specificities of human IgG subclasses is binding of Fc fragment of IgG(1), 2, and 4 but, not IgG(3) to staphylococcal protein A (SPA). This study was conducted to produce, select and characterize a monoclonal antibody (MAb) recognizing human IgG subclasses with specificity similar to SPA. Splenocytes from Balb/c mice immunized with Fc fraction of a human IgG(1) myeloma protein were fused with Sp2/0 myeloma cells. Fused cells were grown in hypoxanthine, aminopterine, and thymidine (HAT) selective medium and cloned by limiting dilution assay. Antibody-secreting cells were screened by enzyme-linked immunosorbent assay (ELISA) and the specificity of secreted MAb was further analyzed, using a panel of purified myeloma proteins by ELISA and immunoblotting. A murine hybridoma designated 6F11E1 was obtained that secretes an MAb specific for the Fc fragment of the immunizing protein. This MAb reacts with isotypic epitope common to IgG(1), 2 and 4 subclasses. An allelic epitope linked to IgG(3) molecules is also recognized by 6F11E1. This pattern of reactivity was found to be highly similar to that of SPA. Our findings imply that similar or overlapping epitopes are recognized by 6F11E1 and SPA.
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