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)

A series of seven monoclonal antibodies recognizing cell surface antigens of similar distribution on a panel of leukemia/lymphoma and lymphoblastoid human cell lines was prepared by hybridoma technique after immunization with non-T, non-B acute lymphoblastic leukemia cell line REH. Immune reactivity of these monoclonal antibodies with B-lymphoblastoid and lymphoma cell lines, as well as with non-T, non-B leukemia cell lines but not with T-leukemic and myeloid leukemic cell lines (with the exception of myeloid leukemia cell line KG 1) was demonstrated by indirect immunofluorescence. No reactivity was observed with the examined human non-hemopoietic tumor cell lines, except melanoma cell lines HMB-2 and SK 1477. These antibodies immunoprecipitated a similar cell surface bimolecular glycoprotein complex consisting of two glycosylated chains (gp30, 35), as demonstrated by immunoprecipitation of cell surface 125I-lactoperoxidase radioiodinated, periodate/tritiated borohydride radiolabeled and 35S-methionine metabolically radiolabeled proteins of REH cells. These properties, typical of MHC class II antigens correspond also to immunoperoxidase staining of lymph nodes with some selected antibodies.
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PMID:Monoclonal antibodies against MHC class II antigens elicited with a human non-T, non-B acute lymphoblastic leukemia cell line. 391 Oct 80

Two newly prepared monoclonal antibodies elicited by a human non-T, non-B acute lymphoblastic leukemia cell line REH recognized distinct antigenic specificities characterized by the pattern of their immunofluorescence reactivities with a panel of hemopoietic cell lines and by immunoprecipitation of 125I-lactoperoxidase radioiodinated cell surface proteins, as well as periodate/tritiated borohydride radiolabeled cell surface sialoglycoproteins. Monoclonal antibody anti-p30 (BraFB6; IgG2b) recognized an antigen similar in its distribution to MHC class II antigens and immunoprecipitated a p30 cell surface protein, radiolabeled by lactoperoxidase catalyzed radioiodination. Monoclonal antibody anti-gp95 (BraEA10; IgG3) reacted in immunofluorescence intensively with non-T, non-B, T-leukemia and myeloid leukemia cell lines, less intensively with lymphoblastoid and lymphoma cell lines of B-phenotype and no reactivity was observed with examined non-hemopoietic human tumor cell lines. This antibody immunoprecipitated a lactoperoxidase radioiodinated and periodate/NaB3H4 tritium-radiolabeled cell surface sialoglycoprotein of approximately 95k (gp95) with variability in its apparent molecular weight, related to the origin of cells utilized for radiolabeling and immunoprecipitation.
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PMID:Hemopoietic cell line distribution and immunoprecipitation of cell surface proteins recognized by two newly prepared monoclonal antibodies elicited by a human non-T, non-B leukemia cell line. 391 Oct 81

The relationship between membrane dynamics and cell growth in human leukemia-lymphoma cell lines of B, T or nonB-nonT phenotype was studied by fluorescence polarization (P) with the probe diphenylhexatriene. Cyclic variations in the degree of P were found as a function of time after subculture. The P value decreases within three hours, until a minimal value obtained before the phase of logarithmic growth. Then, P increases up to its presubculture value. The extent of these variations is not correlated to the differentiation phenotype of the cell lines, nor to their pathologic origin. Experiments with dialyzed or not depleted medium, show that these changes are seen only in the presence of fresh serum. Moreover, the P values vary with the ratio of serum concentration to cell number. These P value modulations are related to subsequent variations in proliferation rate, except in the immature non B-non T REH cells, which grow independently on the serum to cell ratio. It is concluded that changes in the dynamic organization of membrane components are specific for each cell line and are controlled by serum factors.
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PMID:Serum-controlled membrane dynamic changes in growing human leukemia and lymphoma cells. 657 43

The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) was tested for its ability to induce phenotypic changes in the human non-T,. non-B ALL cell line REH. Cells were cultured with nanogram concentrations of TPA for up to 48 hr, and were analyzed by indirect immunofluorescence with a panel of monoclonal antibodies and an antibody to the enzyme terminal deoxynucleotidyl transferase (TdT). TPA induced REH cells to express the leukemia-associated antigen, p24 (detected with monoclonal antibody BA-2; p24/BA-2) by 8 hr of culture, with induction complete by 24 hr. TPA-treated cells also underwent a concomitant decrease in the expression of TdT when analyzed enzymatically or by immunofluorescence. Analysis of TPA-treated cells with monoclonal antibodies BA-1 (detecting a B cell-associated antigen), 7.2 (detecting a monomorphic HLA-DR antigen), or OKT11 (detecting a structure closely associated with the E receptor) showed no change compared to controls. In addition there was no detectable cytoplasmic immunoglobulin in control or TPA-treated cells. These results show clearly that TPA is capable of inducing phenotypic changes in REH cells. Such changes may reflect the differentiation-linked expression of antigens present in normal bone marrow lymphoid progenitor cells.
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PMID:Phorbol ester-induced differentiation of a non-T, non-B leukemic cell line: model for human lymphoid progenitor cell development. 703 64

Cell surface expression of leukosialin (sialophorin, CD43 antigen) on human neoplastic hematopoietic cell lines K-562, U-937, HL-60 and REH was determined with the aid of a new CD43 monoclonal antibody (Bra7G) by the immunochemical (radioimmunoprecipitation, immunoblotting) and immunocytofluorometric techniques. Interferon-gamma and TNF-alpha were utilized as the "physiological" inducers of differentiation-associated markers. The "non-physiological" inducer phorbol ester PMA induced down-regulation of leukosialin cell surface expression on immature erythroid-myeloid leukemia cell line K-562, but up-regulation of CD43 antigen on the promyelocyte leukemia cell line HL-60 and, to a lesser extent on the monocyte-like U-937 and CALLA+ ALL cell line REH. Retinoic acid down-regulated leukosialin on both U-937 monocyte-like cells and the CALLA+ ALL cell line REH. In contrast to these data, interferon-gamma, TNF-alpha, retinoic acid and 1,25(OH)2-vitamin D3 induced the up-regulation of leukosialin in a promyelocytic leukemia cell line HL-60.
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PMID:Modulation of leukosialin (sialophorin, CD43 antigen) on the cell surface of human hematopoietic cell lines induced by cytokins, retinoic acid and 1,25(OH)2-vitamin D3. 835 Sep 52

Adhesion to bone marrow stroma is a key event in normal B lymphopoiesis, allowing exposure of B-cell progenitors to regulatory cytokines. In order to investigate whether similar processes are important in the proliferation of acute lymphoblastic leukaemia (ALL) cells of precursor-B type, the expression of various adhesion molecules was examined. By flow cytometry analysis, CD-44 and the integrins VLA-4 and VLA-5 were the most prominent. CD-44 and VLA-4 were expressed on all 18 cases of precursor-B ALL analysed, while VLA-5 was found on 15 of 18 cases. The integrin CD-11a was detected on 8 of 11 cases, while its ligand, CD-54, was present in 6/12. Other adhesion proteins such as beta 3 integrin, CD-56, CD-15, and Leu8 were not expressed to any significant extent. In view of the known binding of VLA-4 and VLA-5 to extracellular fibronectin (FN), the adhesion of leukaemic cells to FN was evaluated in a colorimetric assay. The precursor-B ALL cell lines REH and KM-3, and 7/15 cases of precursor-B ALL, showed detectable binding to FN. Binding to the other extracellular matrix proteins collagen type 1 and vitronectin was not observed, although two ALL cases showed some binding to laminin. The functional activity of the VLA-4 and VLA-5 molecules was examined using an inhibitory peptide and monoclonal antibodies. These studies indicated that ALL cells adhere to soluble fibronectin predominantly through the VLA-5 molecule (blockable with the PHM-2 antibody and a peptide containing the RGD sequence) although binding mediated by VLA-4 was also apparent in some experiments (blockable by a 40 kDa fragment containing the heparin-binding domain of FN and inhibitory antibodies). These results indicate that precursor-B ALL cells may adhere to marrow stroma through interaction of VLA-4 and VLA-5 with FN, although other mechanisms of adhesion may be important.
Leukemia 1993 Jan
PMID:Adhesion of precursor-B acute lymphoblastic leukaemia cells to bone marrow stromal proteins. 841 84

The BCL-2 gene product is involved in preventing apoptosis. The t(14,18) chromosomal translocation, which results in a fusion messenger RNA containing the entire coding region of BCL-2 and a portion of the immunoglobulin heavy chain gene, is commonly found in follicular lymphoma and appears to play a role in lymphomagenesis by inhibiting cell death. We tested the hypothesis that downregulation of BCL-2 would decrease accumulation of follicular lymphoma cells by treating the t(14,18)-carrying follicular lymphoma cell line WSU-FSCCL in vitro with antisense oligodeoxyribonucleotides (ODNs) directed against BCL-2. We found dose-dependent, sequence-specific inhibition of cell accumulation by an antisense unmodified ODN directed at codons 2 to 7, which downregulated BCL-2 protein levels. This effect was near maximal at an ODN concentration of 40 micrograms/mL (6.9 mumol/L), with minimal toxicity by control sense, reverse, and mutated antisense ODN at the same concentration. The pre-B leukemia cell line REH showed no sequence-specific growth inhibition by the antisense ODN at these concentrations, and BCL-2 protein levels were not altered. These data suggest that WSU-FSCCL may be useful in a murine model to optimize antisense ODN for potential therapeutic utility.
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PMID:Antisense oligodeoxyribonucleotide down-regulation of bcl-2 gene expression inhibits growth of the low-grade non-Hodgkin's lymphoma cell line WSU-FSCCL. 852 64

Double immunofluorescence studies using both surface and cytoplasmic antigens were performed on cells of some human hematopoietic lines. We tested several permeabilization protocols in order to optimize, improve and simplify flow cytometric assay to detect the combinations of two markers present in one cell which could be regarded as leukemia-related markers. It was found, that buffered formaldehyde-acetone (BFA) fixation renders the cell membrane permeable without destroying surface antigens so that intracellular and cell surface markers could be measured simultaneously by flow cytometry. Cell lines used for the experiments reported here included MOLT4 T cell line, mature B cell lines DAUDI and U-266, and early B cell line REH-6. Results from our studies demonstrated, that in the absence of CD3 antigen on the surface membrane of viable MOLT4 blast cells, double labeling of fixed, permeabilized cells revealed 97% mCD7+, cCD3+ double positive cells. Two color staining with anti-CD19 and anti-CD22 monoclonal antibodies (MoAbs) in DAUDI cells showed, that larger part of cCD22+ cells expressed mCD19 antigen. CD22 antigen was absent on DAUDI cell membrane. Of great interest was the finding, that the marker detected by anti-CD19 MoAb which was absent on the membrane of U-266 cells was detected in their cytoplasm. Double staining of these cells revealed, that the number of mCD22+, cCD19+ double positive cells was 80%. Cytoplasmic CD22 antigen along with surface membrane CD19 was used to define early B cell line REH-6 as well. Our results demonstrate majority of double positive cells among tested population (mCD19+, cCD22+). To our knowledge the presence of cytoplasmic IgM detectable by flow cytometry in REH-6 cells, which could be so regarded as a precise and adequate counterpart to pre-B acute leukemia cell phenotype in children, is an original finding. Immunological typing plays an important part in the multiple marker analysis of hematopoietic malignancies. Through these surface and cytoplasmic marker combinations minor neoplastic cell populations could be detected. Human hematopoietic cell lines could serve as a reliable model system for monitoring minimal residual disease in acute leukemia patients.
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PMID:Human hematopoietic cell lines: a model system for study of minimal residual disease detection technique in acute leukemia. 855

A new anti-CD24 immunotoxin (IT), SWA11.dgA, was constructed by coupling the MAb SWA11 via the bivalent linker SMPT to deglycosylated ricin A-chain (dgA). The effects of SWA11.dgA were evaluated in vitro against the B-precursor leukemia cell line REH, the non-B-non-T acute lymphoblastic leukemia cell line NALM-6 and the Burkitt's lymphoma cell lines BL-2 and BL-38. Binding of SWA11 to the CD24 antigen was assessed by flow cytometry demonstrating high affinity of the MAb for all cell lines tested. SWA11.dgA inhibited the protein synthesis of BL-38, NALM-6, REH and BL-2 cells by 50% at concentrations (IC50) of 4.0 x 10(-11) M, 6.0 x 10(-11) M, 8.0 x 10(-11) M and 3.0 x 10(-9) M, respectively. SWA11.dgA was subsequently used for the treatment of disseminated human BL-38 Burkitt's lymphoma in a newly developed SCID mouse model. The mean survival time (MST) of BL-38-bearing SCID mice was extended from 23 days in untreated controls to more than 230 days when 6 microg SWA11.dgA was applied intraperitoneally one day after tumor challenge. All of the animals achieved continuous complete remissions. SCID mice treated with SWA11.dgA 4 days after tumor cell challenge or a reduced dose of SWA11.dgA (67%) also had a significantly extended MST (45.0 and 51.4 days, respectively, as compared to 22.7 and 23.1 days in the controls). We conclude that SWA11.dgA might be of potential use for the treatment of lymphoma in man.
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PMID:Potent anti-tumor effects of an anti-CD24 ricin A-chain immunotoxin in vitro and in a disseminated human Burkitt's lymphoma model in SCID mice. 863 69

The recurrent (12;21)(p13;q22) translocation fuses the two genes TEL and AML1 that have previously been cloned from translocation breakpoints in myeloid leukemias. Using mainly reverse transcriptase-polymerase chain reaction (RT-PCR), the TEL-AML1 chimeric transcript has been observed in 22-27% of pediatric patients with acute lymphoblastic leukemia (ALL), in particular in the early B-lineage ALL subtype, making it the most common genetic lesion in these patients. The vast majority of acute myeloid leukemias, other ALL subtypes and even adults with early B-lineage ALL were TEL-AML1-negative. We determined whether the TEL-AML1 fusion gene can also be observed in continuous human leukemia cell lines with an early B-lineage phenotype. Twenty-nine such cell lines established from children (n = 13) or adults (n = 13) with early B-lineage ALL and five cell lines derived from chronic myeloid leukemia in blast crisis or B cell non-Hodgkin's lymphoma were investigated for the occurrence of the TEL-AML1 rearrangement by RT-PCR. While all 13 adult early B-lineage ALL cell lines and the five cell lines from other leukemias or lymphomas were negative, 1/13 pediatric cell lines (cell line REH) was found to be positive for TEL-AML1; though neither reciprocal AML1-TEL, nor normal TEL, mRNA was detectable by RT-PCR in this cell line. These findings agreed with the results of conventional cytogenetic and FISH analysis of REH which was found to carry the der(21) partner only of t(12;21)(p13;q22), probably resulting from a complex translocation, t(4;12;21;16)(q32;p13;q22;q24.3). Hybridization with flanking cosmid clones (179A6 and 148B6), covering exons 1 and 8 respectively of TEL, confirmed a rearrangement accompanying the t(12;21), and showed cryptic deletion of the residual allele resulting from an apparently reciprocal t(5;12)(q31;p13). These findings in REH provide a further example of, and possible cytogenetic mechanism for, the paradigm of TEL-AML1 fusion accompanied by deletion of the residual TEL allele. The low rate of early B-lineage ALL cell lines carrying this translocation contrasts clearly with the relative high frequency of TEL-AML1-positive cases in primary material. It is possible that expression of the fusion product hampers the in vitro growth and establishment in culture of such leukemic cells. Nevertheless, the cell line REH represents a powerful tool for the further molecular characterization of this unique breakpoint and can serve as a positive control in routine PCR reactions.
Leukemia 1997 Mar
PMID:Occurrence of TEL-AML1 fusion resulting from (12;21) translocation in human early B-lineage leukemia cell lines. 906 87


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