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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of prolonged treatment with antilymphocyte globulin on tumour incidence in BN/a and BN/b mice was studied. One ALG sample appeared to be highly leukaemogenic in two independent experiments. All treated mice developed, after a short latency period, non-thymic lymphomas with involvement of abdominal lymph nodes and spleen resulting in ascites. Three established ascites leukaemia cell lines were examined for the presence of MuLV. In all lines viral C-type particles, soluble viral gs-1 antigen and cell surface antigen related to Gross virus were demonstrated. The mechanism of induction of these tumours remains obscure. Thy hypothetical role of immunosuppression, stimulation of lymphoid cells and activation of leukaemogenic virus is discussed.
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PMID:Leukaemias in BN/a and BN/b mice after prolonged treatment with antilymphocyte globulin. 99 10

The present work has examined the effects of okadaic acid, an inhibitor of type 1 and 2A protein phosphatases, on the regulation of c-jun expression during monocytic differentiation of U-937 leukemia cells. The results demonstrate that okadaic acid treatment is associated with induction of a differentiated monocyte phenotype characterized by: (a) growth arrest; (b) increases in Mac-1 cell surface antigen expression; (c) down-regulation of c-myc transcripts; and (d) induction of tumor necrosis factor gene expression. This induction of monocytic differentiation was associated with transient increases in c-jun mRNA levels, which were maximal at 6 h. Similar effects were obtained for the c-fos gene. Run-on analysis demonstrated detectable levels of c-jun transcription in U-937 cells and that this rate is increased approximately 40-fold following okadaic acid exposure. c-jun mRNA levels were superinduced in cells treated with both okadaic acid and cycloheximide, whereas inhibition of protein synthesis had little, if any, effect on okadaic acid-induced c-jun transcription. The half-life of c-jun mRNA was similar (45-50 min) in both untreated and okadaic acid-induced cells. In contrast, treatment with both okadaic acid and cycloheximide was associated with stabilization (t 1/2 = 90 min) of c-jun transcripts. Taken together, these findings indicate that the induction of c-jun transcription by okadaic acid is controlled primarily by a transcriptional mechanism. Since previous studies have demonstrated that the c-jun gene is autoinduced by Jun/AP-1, we also studied transcription of c-jun promoter (positions -132/+170)-reporter gene constructs with and without a mutated AP-1 element.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of c-jun expression during induction of monocytic differentiation by okadaic acid. 141 3

The Philadelphia (Ph1) chromosome, or its molecular counterpart, the BCR-ABL fusion gene, is a rare but important prognostic indicator in childhood acute lymphoblastic leukemia (ALL), but its impact on adult ALL has not been well ascertained. A prospective study of the BCR-ABL fusion gene was begun on patients entered on clinical trials conducted by the Cancer and Leukemia Group B (CALGB). All patients received intensive, multiagent chemotherapy that included daunorubicin. Over 2 years, 56 patients were studied for molecular evidence of a BCR-ABL gene using Southern blot and pulsed-field gel hybridization analysis. Results were compared with cytogenetic detection of a Ph1 chromosome, and clinical features were compared for the BCR-ABL-positive and -negative groups. Molecular methods detected the BCR-ABL gene in 30% of cases compared with cytogenetic detection of the Ph1 chromosome in only 23%. The majority of cases (76%) showed the p190 gene subtype similar to pediatric ALL; the BCR-ABL-positive cases displayed a more homogeneous immunophenotype than the BCR-ABL-negative cases and were predominantly CALLA positive (86%) and B-cell surface antigen positive (82%). The rate of achieving complete remission was similar in the BCR-ABL-positive and -negative groups (71% and 77%, respectively, P = .72). There were more early relapses in the BCR-ABL-positive group, resulting in a shorter remission duration that was especially marked in the CALLA-positive and B-cell antigen-positive populations. These preliminary data suggest that the impact of the BCR-ABL gene on clinical outcome in ALL may be on maintenance of complete remission (CR) rather than achievement of CR when aggressive, multiagent chemotherapy is used. This study identifies the BCR-ABL gene as an important factor in adult ALL and demonstrates the utility of molecular methods for its accurate diagnosis.
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PMID:Clinical significance of the BCR-ABL fusion gene in adult acute lymphoblastic leukemia: a Cancer and Leukemia Group B Study (8762). 146 14

The anticancer drug mitomycin C (MMC) was conjugated with an affinity-purified murine monoclonal antibody (HI30) to a human T lymphocyte surface differentiation antigen with dextran T-40 as the intermediate carrier. The conjugate (HI30:MMC molar ratio, 1:7) retained full antibody binding activity as determined by an indirect immunofluorescence assay. E. Coli HB101 growth inhibition test showed that the antimicrobial activity [MMC equivalent (microgram/ml)] of the conjugate was about 29.2% as potent as free MMC. In a cytotoxicity test, the conjugate was about 3-10 times more cytotoxic against the antibody-reactive human T lymphocyte leukemia CEM cells than was free MMC or the mixture of HI30 and MMC [IC50 of the MMC equivalent (microgram/ml) was 0.4147, 2.212, 2.171, respectively] and was less cytotoxic against the antibody-nonreactive L1210 cells (IC50 were 1.311, 0.8683, 0.7308, respectively). The selective cytotoxicity was also confirmed by competitive inhibition with free antibody, showing a dependence on antibody binding of the target cell surface antigen. There was no detectable free MMC released from HI30-Dex-MMC conjugate stored at 4 degrees C for over one month as measured by chromatography on a Sephadex G-25 column.
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PMID:[Preparation of a monoclonal antibody (HI30)-mitomycin C conjugate utilizing dextran T-40 and its specific cytotoxicity against human leukemia cell line CEM]. 170 60

A detailed analysis of normal myeloid differentiation was performed using mutlidimensional flow cytometry. Based on two light scattering and three color immunofluorescence signals, the normal maturation pathways of both the monocyte and neutrophil lineages could be elucidated. Gradual changes of light scattering properties and cell surface antigen expression defined the pathways of each of the lineages. The consistency of the location of these lineage specific pathways found in normal individuals provided the basis for the discrimination between normal and leukemic cells in acute myeloid leukemia (ANLL). The position of leukemic cells in patients with ANLL in a five-dimensional space was compared with the position of the maturation tracks in normal individuals. The expression of normal antigens on leukemic cells provided the tools to: (1) distinguish normal from clonal populations of leukemic cells in all 15 patients; (2) detect a lineage predominance, either monocytic or neutrophilic, in all 15 patients; (3) detect maturation heterogeneity in all 15 patients. Although maturation pathways of the monocytic and the neutrophilic lineages were analogous to the normal patterns they were distinct in several ways. The expression of normal antigens on leukemic cells may provide the tools to: (1) obtain a new frame-work for classification of leukemia based on the ability to quantify the aberrant antigen expression and to define a 'distance from normal' based on the characteristics studied (the maturation heterogeneity of the leukemic cells also can be correlated with the clinical outcome of the patients); (2) detect minimal residual disease using the difference in locations of the leukemic cells in the multidimensional space from the normal maturation pathways (3) monitor relapse and changes in phenotypes which may accompany chemotherapy, suggesting the appearance of variant or new clones.
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PMID:Myeloid cell differentiation in normal bone marrow and acute myeloid leukemia assessed by multi-dimensional flow cytometry. 170 34

A monoclonal antibody (MoAB) has been developed which reacts with a previously unidentified hematopoietic cell surface protein called MKW. This MoAB (anti-MKW) does not cluster with antibodies in any of the known cluster groups of differentiation. Blast cell expression of MKW was studied in 196 consecutively diagnosed children with acute lymphoblastic leukemia (ALL), 69 children with previously untreated acute myeloblastic leukemia (AML) and four children with secondary AML. MKW expression, clinical, laboratory and cytogenetic features at diagnosis, and treatment response and duration were examined for significant correlations. MKW was expressed on blasts from 12.8% of children with ALL and 24.6% of children with de novo AML. The expression of MKW appears to be more common in patients with secondary AML (three of four) than de novo AML (17 of 69). In patients with AML, the expression of MKW was correlated with an elevated initial leukocyte count (p = 0.0005) and poorer disease-free survival (p = 0.04). In patients with ALL, the expression of MKW was associated with a lower hemoglobin level (p less than 0.05) and a lower complete remission rate (p = 0.02). At a median follow-up of 4.6 years ALL patients with greater than or equal to 50% MKW+ blasts had a poorer event-free survival (EFS) than both MKW+ patients with 25-49% positive blasts (p = 0.03) and MKW+ patients (p = 0.0001). The disease-free survival was also poorer for ALL patients with greater than or equal to 50% MKW+ blasts (p = 0.02). In Cox regression analysis, the expression of MKW had an independent prognostic significance in children with ALL. As MKW is a unique cell surface antigen and its expression has prognostic significance in acute leukemias in children, further study in a larger series of patients is warranted.
Leukemia 1991 Jan
PMID:Expression of a novel surface antigen MKW in childhood acute leukemia has prognostic significance. 199 57

To investigate cell surface antigens of activated human eosinophils using monoclonal antibodies, we established a murine anti-human eosinophil monoclonal antibody AE500 by immunizing with blood eosinophils from patients with idiopathic hypereosinophilic syndrome (HES) and characterized the reactivity to a variety of human leucocytes by a fluorescence-activated cell sorter. AE500 reacted with blood eosinophils and neutrophils in nine out of 11 patients with marked eosinophilia (greater than or equal to 2500/microliters) (seven with idiopathic eosinophilia including HES and two with asthma), but not with those in asthmatic patients with mild eosinophilia (n = 10) or in healthy subjects (n = 8). AE500 did not react with blood lymphocytes, monocytes or platelets. AE500 did not react with human myeloid or lymphoid cell lines, including eosinophilic leukemia cell lines EOL-1 and EOL-3. The reactivity of AE500 to blood eosinophils and neutrophils in patients with marked eosinophilia changed in relation to blood eosinophil counts and prednisolone therapy. In addition, the reactivity of AE500 to blood eosinophils was increased in three out of four AE500-positive eosinophils by the incubation of the cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) at 37 degrees C for 30 min, but not with interleukin 3 or interleukin-5. These results suggest that the anti-eosinophil antibody AE500 detects a cell surface antigen expressed on blood granulocytes in a hypereosinophilic state. This anti-eosinophil antibody would be useful for analysing the mechanism of eosinophilia.
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PMID:Characteristics of an anti-eosinophil monoclonal antibody that recognizes granulocytes from patients with blood eosinophilia but not from subjects without eosinophilia. 202 54

Acute leukemias are classified using the morphological and cytochemical criteria set forward by the French, American and British (FAB) group. Immunophenotyping is helpful for the differential diagnosis but is secondary to the morphological criteria. Immunophenotyping performed by flow cytometry, however, can yield valuable information on cell morphology in addition to cell surface antigen expression. To provide a basis of a combined evaluation of both morphology, i.e. light scattering, and immunophenotype by flow cytometry we have compared the light scattering profiles of 70 patients newly diagnosed with acute leukemia with normal bone marrow and related the findings to the FAB classification. Three main light scattering profiles were observed in the bone marrow aspirates of the 70 patients (A1,2; B1,2,3; C1,2,3,4). A1,2, characterized by a predominant cell cluster with low forward and orthogonal light scattering, contained only and all patients diagnosed as acute lymphoblastic leukemia, acute undifferentiated leukemia, and acute non-lymphocytic leukemia M6 and M1. B1,2,3 is characterized by a predominant cell cluster with large forward and low to high orthogonal light scattering. Category B1 contained the majority of patients classified as M5; the M3 leukemias were categorized as B2. C1,2,3,4 is characterized by a predominant cell cluster with low forward and orthogonal light scattering that branches towards regions with larger light scattering. Categories C1 and C2 contained the majority of the patients classified as M2. Category C3 was specific for M4 and M4eo leukemias. The patients diagnosed as M4 were heterogeneous and equally distributed over the B and C categories. The clear relationship found between the FAB classification and classification by the light scattering profile of the acute leukemias enhances the importance of the flow cytometric classification of leukemias. In contrast with light microscopy, flow cytometry can now provide the hematologist with an objective technique to classify leukemias by the simultaneous assessment of cell surface antigen expression and cell morphology, i.e. light scattering.
Leukemia 1991 Apr
PMID:Flow cytometric characterization of acute myeloid leukemia. Part 1. Significance of light scattering properties. 202 98

We describe the properties of three monoclonal antibodies (McAbs) (21H73, 37G7 and 49C12) against K562 cell surface antigens correlated with differentiation induced by 12-O-tetradecanoyl phorbol-13-acetate (TPA). Each of the McAbs immunoprecipitated K562 cell surface antigen with molecular weight (MW) of approximately 51 kD, 82 kD or 92 kD, respectively. The antigens detected by McAbs 21H73 and 37G7 were not immunoprecipitated from K562 cells differentiated into monocyte-macrophages by TPA (K562-TPA). On the other hand, 49C12 immunoprecipitated an antigen with MW of 92 kD from K562-TPA cells, but not from undifferentiated K562 cells. To examine the distribution of these antigens among human haematopoietic stem cells, bone marrow cells were separated by the panning method using these McAbs and subjected to colony-forming assays. The McAb 21H73 reacted with CFU-mix and BFU-E but with neither CFU-E nor CFU-GM. CFU-mix and BFU-E were enriched approximately 6.2-14.7-fold and 2-fold by the panning procedure using 21H73, respectively. On the other hand, 37G7 reacted only with BFU-E, and 49C12 reacted with CFU-GM but not with any other haematopoietic progenitor cells. We also examined the reactivity of these McAbs with leukaemia cells freshly isolated from 26 patients. The antigen defined by 21H73 was not expressed on any leukaemia cells from patients except for cells from an acute lymphocytic leukaemia (ALL, L3) and a CML in blastic crisis. The McAb 37G7 reacted with several types of leukaemia cells. The antigen defined by 49C12 was expressed on almost all leukaemia cells isolated from patients. These results suggest that 21H73 allows purification and enrichment of normal haematopoietic pluripotent stem cells from both normal and leukaemia patients' bone marrow specimens, especially following the step to remove leukaemia cells and haematopoietic progenitor cells other than CFU-mix by using 37G7 and/or 49C12.
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PMID:Monoclonal antibodies raised against K562 cells reacted with human haematopoietic pluripotent stem cells. 203 Jun

We describe the haematological findings and clinical course of a 15-year-old male who presented with a spontaneous acute lymphoblastic leukaemia. The lymphoid origin of the leukaemia was supported by cell surface antigen studies and immunoglobulin heavy chain gene analysis. Bone marrow karyotype was simple monosomy 7 and the lymphoblasts expressing the myeloid associated antigen CD 33. Both of these features have been previously shown to indicate a poor prognosis. The findings in this patient support a previous hypothesis that monosomy 7 can arise at the stem cell level.
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PMID:Monosomy 7, leukaemia and immunoglobulin heavy chain gene rearrangement. 211 32


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