Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

beta 2-Microglobulin is a low molecular weight protein that is found in most biological fluids. It was originally isolated from urine of cadmium-poisoned patients. Its amino acid sequence was established and shown to be structurally related to immunoglobulin constant domains. With the aid of antibodies specific against beta 2-microglobulin, the protein was detected on the membranes of all nucleated cells, normal and neoplastic. Measuring the quantity of beta 2-microglobulin showed that high levels are present in patients with renal tubular deficiencies and several other pathological conditions including neoplastic diseases. Extremely high levels were detected in seminal fluid and colostrum. Despite the structural relationship to immunoglobulins, no immunological relationship was demonstrated with these proteins using antibodies specific for beta 2-microglobulin. However, such antibodies are cytotoxic to all cells carrying beta 2-microglobulin on their surfaces. The discovery that beta 2-microglobulin is an integral part of the histocompatibility antigens of human and murine origin stimulated further research and interest in this molecule. Several groups of investigators have shown that beta 2-microglobulin is the low molecular weight chain and is noncovalently bound to a high molecular weight chain which carries the histocompatibility antigens. The structure of the histocompatibility antigens of lymphocytes (HLA) was shown by immunochemical as well as biological methods, and it is now well accepted. The antibodies against beta 2-microglobulin are extremely useful in the isolation of the histocompatibility antigens for sequence studies. Furthermore, the antibody to beta 2-microglobulin revealed that other structures may be bound to beta 2-microglobulin such as phytohemoagglutimin (PHA) receptors, mixed lymphocyte culture (MLC) antigens, etc. Murine thymus leukemia (TL) antigen also contains beta 2-microglobulin as an integral part of its structure; other tumor antigens may have a similar structure. Through all these studies, beta 2-microglobulin emerged as the best known membrane protein that can serve as a model for study of the arrangement and the function of the cell membrane.
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PMID:beta 2-Microglobulin: methods and clinical applications. 8 22

Cell membrane components that contain beta 2-microglobulin were purified from cells of a human T cell-type leukemia cell line, HPB-ALL. They contained membrane components that have the same molecular size and the same subunit structure as HLA(A,B,C) antigens but are separable from the typical beta 2-microglobulin-containing cell membrane components, i.e., the HLA (A,B,C) antigens, by xenoantibody reagents. A sensitive radioimmunoassay was constructed for detection of the T cell membrane components. The assay revealed that the cell membrane components are expressed exclusively on cells of T cell-type leukemia cell lines among the human lymphoid cell lines tested, predominantly in thymus, among the human organs and tissues tested. They were not present on cells of human B cell-type cell lines or on cells of nonlymphoid organs and tissues. No alloantibodies directed to the T cell membrane components, the putative human homologues of mouse TL antigens, were found in any of the human tissue typing sera tested.
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PMID:Human cell membrane components dominant in T cell lineage: identification and characterization of human TL-like antigens. 38 77

To identify the cellular receptors and other cell surface molecules playing essential roles in the transmission of human T-cell leukemia virus type 1 (HTLV-1), we have been isolating monoclonal antibodies (mAbs) that are capable of inhibiting HTLV-1-induced syncytium formation. In the present study, we isolated two mAbs, H11 (IgM) and H14 (IgG1), inhibitory to syncytium formation in the coculture of TOM-1 or C91/PL (both HTLV-1-positive human T-cell lines) and MOLT-4/8 (HTLV-1-negative human T-cell line) by immunizing the membrane fraction of human osteosarcoma line HOS. By immunoprecipitation and immunoblotting, H11 and H14 were found to be specific for MHC class I heavy chain and beta 2-microglobulin (beta 2 M), respectively. Among the four commercially obtained mAbs, two mAbs for MHC class I antigen and two mAbs to beta 2 M, one mAb to MHC class I antigen and one mAb to beta 2 M were also found to be inhibitory to the syncytium formation. The functional comparison of these mAbs revealed that the syncytium-inhibitory mAbs induced strong homotypic cell adhesion particularly in the HTLV-1-positive T-cell lines. This cell adhesion was dependent on temperature, energy metabolism, and microfilament function but not on the activity of protein kinase C or divalent cations. These results suggest a novel type of LFA-1-independent cell adhesion induced by signal transduction via MHC class I antigen.
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PMID:Induction of strong homotypic adhesion in human T cell lines positive with human T-cell leukemia virus type 1 by monoclonal antibodies to MHC class I and beta 2-microglobulin. 138 Aug 95

Serum levels of beta 2-microglobulin (S-B2m) were analysed at diagnosis in 69 cases of acute myeloid leukemias (AML) as a possible prognostic indicator. S-B2m was correlated to various clinical and laboratory features and with respect to response to chemotherapy and following clinical outcome. S-B2m was found to be increased (greater than 3 mg/l) in 40.6% of tested patients and, in particular, in the monocytic variants (M4, M5) of AML (4.2 versus 2.3 mg/l, p less than 0.01). S-B-B2m values paralleled white blood cell count, serum lysozyme levels and expression of monocytic membrane markers at presentation, but no correlation was found with age, renal function or immunological myeloid antigens. Increased levels of S-B2m were associated with a lower likelihood of obtaining a complete remission (25 versus 58.5%, p less than 0.01), while in the multivariate analysis S-B2m greater than 3 mg/l and white blood cell count greater than 20 x 10(9)/l were independent variables significantly influencing disease-free survival in responsive patients (five years DFS for S-B2m greater than or less than 3 mg/l: 28 versus 62%, p less than 0.05). In conclusion, the measurement of S-B2m at diagnosis may have prognostic relevance in AML.
Leukemia 1992 Oct
PMID:Prognostic relevance of serum beta 2-microglobulin in acute myeloid leukemia. 140 62

Differentiation choices in the haemopoietic and nervous systems are controlled in part by instructive factors. The cholinergic differentiation factor (CDF, also known as leukaemia inhibitory factor, LIF) affects the development of cultured cells from both systems. To understand the role of CDF/LIF during normal development in vivo, we have begun to localize its mRNA in the late fetal and postnatal rat. Application of reverse transcriptase-polymerase chain reaction and RNase protection methods reveals that CDF/LIF mRNA levels are developmentally modulated in both haemopoietic and neural tissues. A target tissue of cholinergic sympathetic neurons, the footpads that contain the sweat glands, express high levels of this mRNA (relative to mRNA for actin and beta 2-microglobulin). Levels in targets of noradrenergic neurons are lower, but do undergo significant changes during development. Signals are also detected in selective regions of the adult brain, and in embryonic skeletal muscle. This finding in muscle may be significant for motor neurons, because CDF/LIF is a trophic factor for these neurons in culture. Embryonic liver, neonatal thymus and postnatal spleen express CDF/LIF mRNA, and expression in gut is the highest of all tissues examined. The selective tissue distribution and developmental modulation of CDF/LIF mRNA expression support a role for this factor in the normal development of several organ systems.
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PMID:Further studies of the distribution of CDF/LIF mRNA. 142 9

In our previous study, we found that serum beta 2-microglobulin (beta 2M) levels were elevated in the active, but not in the inactive, phase of adult T-cell leukemia (ATL), suggesting a correlation between the beta 2M level and the clinical severity of this disease. In this study we examined the mechanisms underlying the elevation of serum beta 2M levels in ATL. First, the production of beta 2M by ATL cells was investigated in vitro. High levels of beta 2M were detected in the conditioned culture medium (CM) of ATL cells from seven out of nine patients. Second, we assessed the effects of the CM on the release of beta 2M by three human cell lines unrelated to ATL (NCTC 2544, Chang liver, and L 132; originating from the skin, the liver, and the fetal lung, respectively). Most of the CM definitely promoted beta 2M production by these cell lines. beta 2M production by the cell lines was markedly promoted by exogenous interferon-gamma (IFN-gamma), a well-known potent inducer of class I HLA antigen expression. We then investigated whether an antibody directed against IFN-gamma could attenuate the activity of three ATL CM. The anti-IFN-gamma antibody reduced the stimulatory activity of the CM to 28-65% of the original level, but did not affect basal beta 2M production by these cell lines. These data suggest that there are at least two mechanisms causing the elevation of serum beta 2M levels in ATL; direct production by tumor cells, and production by non-malignant cells that is mediated via humoral factors secreted by the ATL cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Possible mechanisms for the elevation of serum beta 2-microglobulin levels in adult T-cell leukemia. 151 Nov 67

Monoclonal gammopathy of type IgG-lambda (IgG concentration 27.8 g/l) was discovered by chance in a 66-year-old woman with aortic and mitral valve disease. The patient declined any further diagnostic procedures. Three months later she experienced severe pain in the lumbar spine and developed decompensated cardiac failure with pulmonary and ankle edema. The IgG concentration had risen to 50.5 g/l. Echocardiography showed a large pericardial effusion and 600 ml of bloodstained fluid containing numerous plasma cells was aspirated (total protein 81.8 g/l, gamma-globulin 38.9%). Iliac crest biopsy showed diffuse infiltration with polymorphic plasma cells, but the differential count in peripheral blood was unremarkable. Multiple myeloma of Stage IIa was diagnosed and she was given cytostatic therapy with 17.5 mg melphalan and 112 mg methylprednisolone daily by mouth (for 4 days at intervals of 6 weeks). Though at first the IgG concentration fell, it later rose again. The beta 2-microglobulin level was raised at 30 mg/l. After three cycles of chemotherapy the patient complained of severe pain in the hips and thighs. The blood film now showed numerous, predominantly immature plasma cells. A few days later, having been ill for four months in all, she died, showing all the signs and symptoms of plasma cell leukaemia.
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PMID:[IgG-lambda-type multiple myeloma with plasma-cell pericardial effusion and terminal plasma-cell leukemia]. 142 69

The cDNA encoding the murine CD1.1 and CD1.2 gene products were isolated and their complete nucleotide sequence was determined. The nucleotide sequence and genomic organization of these molecules were similar to human CD1. The sequences in the alpha 1- alpha 3 domains were almost identical to previously reported genomic clones from a different strain, indicating limited polymorphism among these molecules. The predicted amino acid sequence in the transmembrane region and in the cytoplasmic tail was identical for CD1.1 and CD1.2. The two cDNA were also homologous in the 5' untranslated region but diverged in the 3' untranslated region. In contrast to human CD1, which is expressed at high levels in thymus, the expression of CD1 message in murine thymus was not detected in either thymus leukemia Ag positive or negative strains. Cell expressing murine CD1.1 were generated after transfer of the CD1.1 cDNA into murine cell lines. Immunoprecipitation with a rat anti-mouse CD1.1 mAb showed that the transfected CD1 was expressed on the cell surface as a beta 2-microglobulin-linked heterodimer. These results demonstrate that the murine and human CD1 genes, although encoding homologous transmembrane glycoproteins, are expressed in distinct tissues and may serve different functions.
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PMID:Isolation and expression of cDNA encoding the murine homologues of CD1. 170 17

Ten hairy-cell leukemia patients were treated with interferon beta (IFN-beta) at a dose rate of 2 x 10(6) IU/m2 x 5 days for 4 weeks (induction therapy) and, thereafter, at the same dose three times a week for 11 months (maintenance therapy). The effect of this treatment on serum neopterin, beta 2-microglobulin, (2'-5')oligoadenylate [(2'-5')An] levels, intracellular (2'-5')An values and human Mx protein synthesis was analysed. There were significant rises in serum neopterin and (2'-5')An levels during both induction and maintenance, whereas beta 2-microglobulin levels rose only during induction. Rises in intracellular (2'-5')An were documented mainly during induction, but they were not significantly higher than pretherapy values. IFN beta provoked an increase in human Mx protein synthesis over the entire induction-maintenance period, but was only significantly higher than baseline during induction. All markers proved useful for monitoring the effects of IFN beta dose schedules, but were not predictive of clinical outcome. Natural killer activity and IFN gamma production, which were initially defective, followed a different trend from that of the other factors studied, in that increases were documented only late in the course of therapy when the disease was already in remission.
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PMID:Biochemical and immunological responses of hairy cell leukemia patients to interferon beta. 176 Aug 15

Thirty-seven patients with adult T-cell leukemia had serum beta 2-microglobulin (beta 2M) estimated at presentation. A significant association was found between beta 2M and the subtypes of the disease: beta 2M in the acute type is significantly higher than in the chronic and smoldering types (p less than 0.01), and beta 2M in the lymphoma type is apparently higher than in the chronic and smoldering types, although the difference between the lymphoma and chronic types was not statistically significant. An apparent reduction in beta 2M levels after chemotherapy was observed in 7 patients who reached partial or complete remission. One patient who was resistant to chemotherapy showed elevated beta 2M values even after intensive chemotherapy. In another patient, who attained partial remission with a concordant reduction in beta 2M, renewed elevation of beta 2M was observed in parallel with exacerbation of other parameters such as lactate dehydrogenase (LDH), WBC, calcium and clinical manifestations. Correlation analysis was carried out between beta 2M, LDH, calcium, lymphoid cell count and the grade of clinical severity. The beta 2M level was moderately correlated with LDH, calcium, the grade of clinical severity but not with the lymphoid cell count. The clinical severity also correlated with LDH and calcium but to a lesser extent than with beta 2M. These data support the use of the beta 2M in the evaluation of adult T-cell leukemia.
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PMID:Serum beta 2-microglobulin in patients with adult T-cell leukemia. 195 Mar 59


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