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)

The human T6 antigen was studied by two monoclonal antibodies: OKT6 and Leu-6. A third monoclonal antibody, C56 (developed in our laboratory), was found to have similar properties to those of OKT6. On SDS-PAGE, all three antibodies precipitated a 48,000-12,000-dalton heterodimer. Two-dimensional gel electrophoresis and chymotryptic peptide map analysis revealed that these antibodies precipitated in identical 48,000-dalton heavy chain which was distinguishable from the HLA-A,B,C heavy chains. The single 12,000-dalton light chain precipitated with OKT6 antibody was shown to be distinct from beta 2-microglobulin by its pI. The two light chains precipitated with Leu-6 antibody were resolved by charge into beta 2-microglobulin and the more basic 12,000-dalton peptide identical to that precipitated with OKT6. In addition to beta 2-microglobulin, the latter component (presumably beta t) was also found in the light-chain fraction precipitated from the thymocytes with a monoclonal antibody recognizing the framework of HLA-A,B,C heavy chains. Using chymotryptic peptide mapping, no polymorphism was detected among the heavy chains of the T6 antigen isolated from thymocytes of four individuals. All three monoclonal antibodies failed to precipitate murine TL from ASL1 leukemia cell lysates. Similarly, none of the six monoclonal and two conventional anti-TL antibodies reacted with T6. Although a high degree of homology was found by peptide map analysis among the TL molecules encoded by the Tlaa, Tlad and Tlae alleles, a comparison between their peptide maps and that of T6 revealed no similarity. Despite previous suggestions that T6 is homologous to murine TL, the present biochemical studies do not support this hypothesis.
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PMID:Biochemical characterization of the human T6 antigen: a comparison between T6 and murine TL. 643 95

A monoclonal antibody, M241, was produced which binds to a human cell surface molecule with properties similar to the murine thymus leukemia (TL) antigen. This human TL-like antigen was found on thymocytes and some T cell lines derived from patients with acute lymphocytic leukemia, but was not found on peripheral blood lymphocytes or B cell lines. The monoclonal antibody M241 was used to immunoprecipitate a molecule from lysates of 125I surface-labeled MOLT 4 cells which had two subunits, a 43-kDa chain and a 12-kDa chain. The small subunit was shown to be beta 2-microglobulin (beta 2m) by immunoprecipitation with a monoclonal antibody, BBM.1, which recognizes human beta 2 m. The TL-like molecule recognized by M241 was shown to be serologically distinct from the HLA-A,B,C molecules recognized by three monoclonal antibodies W6/32, PA2.6 and BB7.8, and distinct from another human thymocyte antigen, the 49 kDa HTA 1 molecule, recognized by the monoclonal antibody NA1/34. Following removal of the HLA-A,B,C molecules, the HTA 1 molecules, and the M241-defined TL-like molecules from MOLT 4 lysates, additional beta 2m-associated molecules were immunoprecipitated with BBM.1. These molecules contained a 45-kDa subunit attached to beta 2m.
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PMID:A monoclonal antibody recognizing a human thymus leukemia-like antigen associated with beta 2-microglobulin. 675 87

The region of chromosome 2 between H-13 and H-3 has been shown to contain loci coding for a variety of other alloantigens, including Ly-4 and the locus coding for beta 2-microglobulin. Herein we show that Ly-6 and Ly-11 are coded for by genes in a segment of chromosome 2 adjacent to the H-3-H-13 region and that this segment of chromosome also contains the tightly linked loci coding for antigens Ala-1, DAG, H9/25, H-30, Ly-8, and ThB. In addition, at least one locus (and probably more) affecting susceptibility to leukemia induction is found within this gene cluster.
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PMID:Evidence for a major cluster of lymphocyte differentiation antigens on murine chromosome 2. 696 23

Three human thymic cell-surface antigens T6, T9 and T10, previously defined by monoclonal antibodies, were analyzed using immunoprecipitation techniques. The antigen T6 was found to be a 49,000 dalton glycoprotein, which is associated with beta 2-microglobulin, the small subunit (12,000 daltons) of the HLA-A, -B, and -C antigens. The target antigen for the monoclonal reagent anti-T9 was found to be a glycoprotein of 94,000 daltons, which appears as a disulfide-linked dimer of 190,000 daltons on the cell surface. The antigen precipitated by the anti-T10 antibody is a 45,000 dalton glycoprotein. We present preliminary evidence that all three cell-surface proteins may be integral membrane proteins. These findings, in addition to the distribution patterns, suggest that the T6 antigen is the human homolog of the murine thymus leukemia (TL) antigen.
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PMID:Biochemical studies of the human thymocyte cell-surface antigens T6, T9 and T10. 701 88

Charge heterogeneity of the human thymocyte antigen T6 was studied by isoelectric focusing and two-dimensional gel electrophoresis. The larger subunit of T6 (a 49,000 m.w. glycoprotein) contained several oligosaccharide side chains bearing up to 12 terminal sialic acids. When T6 antigens from 19 individual thymuses were analyzed, no differences in the isoelectric focusing patterns of the larger subunit could be detected. The larger subunit of the T6 antigen from MOLT-4 cells (52,000 m.w.) contained an extra oligosaccharide if compared with the T6 antigen from thymus or three other T leukemic cell lines. Two types of small subunits of T6 were found. In addition to a protein of m.w. 12,000, pI 5.5 identified as beta 2-microglobulin, a (m.w. 12,000, pI 7.0) nonglycosylated protein, was detected on two dimensional gels. This protein does not cross-react with beta 2-microglobulin, and its amount varied in different T6 preparations. The tissue distribution, the m.w. the association with beta 2-microglobulin, and the limited structural heterogeneity of T6 support the idea that T6 is the human homologue of the murine thymus leukemia antigen (TL).
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PMID:Further biochemical characterization of the human thymocyte differentiation antigen T6. 703 76

Messenger ribonucleic acid (mRNA) for thymus-leukemia antigens, membrane-associated glycoproteins of murine leukemia cells, was obtained from polysomes of murine leukemia cells forming thymus-leukemia antigens. Polysomes forming thymus-leukemia antigens were recovered by immunoprecipitation using alloantibodies specific for the 1,2,3 determinants of the thymus-leukemia antigen complex before they were extracted with phenol-detergent. Poly(adenylic acid)-containing RNA [poly(A)-RNA] was fractionated by oligo[deoxythymidylate] [oligo(dT)]-cellulose chromatography. The mRNA obtained had a sedimentation coefficient of approximately 17 S in agreement with the predicted size necessary for forming proteins specifying thymus-leukemia antigens. In a wheat germ system, the polypeptides formed upon addition of mRNA for thymus-leukemia antigens consisted of a major product with a molecular weight of 42,000. It was larger than the nonglycosylated heavy chain molecule of 40,000 daltons formed by the cells themselves. On the cell surface thymus-leukemia antigens exist as glycosylated molecules of 47,000 daltons associated with a light-chain equivalent to beta 2-microglobulin. Molecules of 40,000 daltons were isolated from the cells cultured in the presence of tunicamycin, an inhibitor of de novo glycosylation, and by treating thymus-leukemia heavy chains with endo-beta-N-acetylglucosaminidase H.
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PMID:Isolation and cell-free translation of messenger ribonucleic acids specifying thymus-leukemia antigens. 745 38

Serum levels of lactate dehydrogenase (LDG) and beta 2-microglobulin (beta 2-MG) were measured in 164 and 128 patients with multiple myeloma (MM), respectively. High levels of LDG were recordable in 15.4% of patients at diagnosis and 36.8% of terminal stage patients. The frequency of extraosseous foci in untreated patients with high LDG activity made up 36.8%, survival median 19 months. In normal LDG activity the above values were 6.8% and more than 36 months, respectively. The highest LDG level occurred in patients with terminal plasmic cell leukemia. MM with IgD secretion was characterized by a a more frequent rise in LDG concentrations. Normal LDG amounts in active MM were seen in 58 (54.2%) out of 107 patients. beta 2-MG levels exceeded 6 mg/l in 75 of 128 patients with normal creatinine. These patients had a short survival median 24 months. Those patients who had beta 2-MG levels under 6 mg/l have not reached survival median for 36 months of follow-up. The authors hold that beta 2-MG concentrations are of prognostic value in all myeloma secretions and in nonsecretory myeloma as well though their indications are not absolute as 14% had low beta 2-MG levels in high MM activity. Comparative results are presented for 40 high-risk MM patients. Group 1 (20 patients) have received standard chemotherapy. Group 2 (20 patients) have undergone intensive polychemotherapy. Survival median made up 12 and 26 months for group 1 and 2, respectively.
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PMID:[The significance of lactate dehydrogenase and beta 2-microglobulin levels for the assessment of the prognosis and choice of therapy in multiple myeloma]. 748 3

We investigated the clinical significance of the serum soluble interleukin-6 receptor (sIL-6R) in 42 patients with plasma cell dyscrasias (27 with multiple myeloma (MM), 13 with monoclonal gammopathy of undetermined significance (MGUS), and two with plasma cell leukaemia (PCL)). Serum levels of sIL-6R in normal individuals were 77 +/- 21 ng/ml (mean +/- SD, n = 18); those in patients with MGUS and with MM were elevated (102 +/- 33 ng/ml, mean +/- SD, P < 0.05 and 126 +/- 60 ng/ml, mean +/- SD, P < 0.01, respectively). Significant correlations were not found between the serum levels of sIL-6R and known prognostic factors (C-reactive protein, haemoglobin levels, calcium, creatinine, beta 2-microglobulin, amounts of M-protein, or percentages of plasma cells in bone marrow). Elevated serum sIL-6R did not affect the survival of the patients with MM. Serial measurements of sIL-6R together with the clinical course of patients with plasma cell neoplasias revealed a good correlation between the sIL-6R level and disease activity. We conclude that sIL-6R can be used as a clinical factor correlated with the disease activity, at least in some patients with plasma cell neoplasias.
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PMID:Clinical significance of elevated soluble interleukin-6 receptor levels in the sera of patients with plasma cell dyscrasias. 861 53

To clarify the clinical and biological significance of beta 2-microglobulin (beta 2-M) in serum of adult T cell leukemia (ATL) associated with human lymphotropic virus type-I (HTLV-I), beta 2-M was measured in 52 patients with ATL (acute ATL, 35 patients; lymphoma ATL, two patients; chronic ATL, 12 patients; smoldering ATL, three patients), and it was compared with serum lactic dehydrogenase (LDH). Statistical analysis disclosed a correlation between beta 2-M level and the percentage of abnormal lymphocytes (P < 0.05) and platelet count (P < 0.01). There was a correlation between LDH and platelet count (P < 0.01), and a tendency of correlation between LDH and the percentage of abnormal lymphocytes (P < 0.15). Significant difference was present in beta 2-M as well as LDH between acute ATL and chronic ATL (P < 0.01), and between acute ATL and smoldering ATL (P < 0.01). We also investigated a significant inverse correlation between beta 2-M level as well as LDH level and the length of survival after the initial diagnosis (P < 0.01). Thus, the beta 2-M level may indicate the aggressiveness of ATL cells and predict the length of survival.
Leukemia 1995 Apr
PMID:Clinical significance of beta 2-microglobulin in serum of adult T cell leukemia. 772 90

Mouse thymus-leukemia antigen (TL), like other major histocompatibility complex (MHC) class I-b antigens, displays signs of a specialized function. It is normally expressed at high levels on immature thymocytes and at moderate levels on gut epithelium and activated mature T cells. A promoter/enhancer region unique among class I genes accounts for this narrow range of tissue distribution. Like most other class I molecules, TL is dependent upon endogenous beta 2-microglobulin (beta 2m) for transport to the surface. However, here we show that unlike most other MHC class I molecules, TL is expressed efficiently in the absence of functional transporter associated with antigen processing subunit 2 (TAP2). A putative fourth TLa gene cloned from A.SL1 cells was expressed in RMA and RMA-S cells. In bulk transformants, TL expression is higher in TAP2-RMA-S cells than in wild-type RMA cells, and is not elevated by incubation at reduced temperatures or exposure to exogenous beta 2m. Analysis of immunoprecipitated molecules by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate indicates that TL is processed normally in RMA-S cells and is associated with beta 2m both intracellularly and at the cell surface. However, TL heavy chains expressed on the cell surface in the absence of TAP2 are cleaved to a predominant 38 kDa fragment, presumably the result of an altered conformation that renders TL more susceptible to proteolysis. These results suggest that while TL may normally acquire TAP2-dependent peptides, this class I-b molecule does not require them for efficient export to, and stable expression at the cell surface.
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PMID:Surface expression of beta 2-microglobulin-associated thymus-leukemia antigen is independent of TAP2. 773 70


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