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

Fresh leukaemia cells from the peripheral blood of 6 patients with B-chronic lymphocytic leukaemia (CLL) were cultured in the continuous presence of the phorbolester 12-O-tetradecanoylphorbol 13-acetate (TPA) for in vitro induction of differentiation. Upon treatment with TPA the cells showed distinct morphological changes consisting of cytoplasmic and nuclear enlargement, vacuolisation and protrusion of cytoplasm, eccentric location of nuclei with perinuclear clear zones, and oval to elongated cell forms. Isoenzyme profiles of the enzymes carboxylic esterase, acid phosphatase, hexosaminidase and lactate dehydrogenase (LDH) were analysed by isoelectric focusing on polyacrylamide gels. An increase in the number and in the staining intensity of isoenzymes were observed for all 4 enzymes in the TPA-exposed cells indicating a maturation along the B cell pathway. TPA triggered the new expression of the tartrate-resistant acid phosphatase isoenzyme, a marker of hairy cell leukaemia (HCL) cells, and of the hexosaminidase I isoenzyme, a marker of multiple myeloma cells. The induced phenotypic changes are suggestive of differentiation to stages corresponding to those of HCL cells or 'pre-plasma cells'.
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PMID:Morphological and isoenzymatic differentiation of B-chronic lymphocytic leukaemia cells induced by phorbolester. 348 41

The ability of 12-O-tetradecanoylphorbol 13-acetate (TPA) to induce stable phenotypic changes that serve as markers of differentiation was examined in the non-T/non-B leukemia cell lines KM-3 and REH and in the pre-B leukemia cell lines BV-173 and NALM-6. Isoenzymes of the enzymes carboxylic esterase, acid phosphatase, hexosaminidase, and lactate dehydrogenase (LDH), separated by isoelectric focusing on horizontal polyacrylamide thin-layer gels, were used to monitor induced changes. TPA in different concentrations completely or partially inhibited cell proliferation, but had no drug-related cytotoxicity. No increase in the number of nitro-blue-tetrazolium-reducing cells nor adherence to plastic surface was found. In all four cell lines, TPA caused an increase in number and staining intensity of esterase, acid phosphatase, and LDH isoenzymes. The resulting isoenzyme profiles corresponded to those seen at more mature intermediate stages of B-cell proliferation, but did not indicate a terminal differentiation to mature B cells. The loss of the hexosaminidase I isoenzyme, which is a marker of immature hematopoietic cells, was a further indicator of induced maturation. These results demonstrate that while TPA is capable of inducing various immature non-T/non-B and pre-B cell lines to differentiate, the differentiation progression appears to be restricted to intermediate stages, in contrast to the terminal differentiation inducible in myeloid cells.
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PMID:Pre-B and non-T/non-B leukemia cell lines BV-173, KM-3, NALM-6, and REH: changes in isoenzyme profiles during induction of differentiation. 348 15

Biochemical analysis has been used to monitor the induction of differentiation in cultured human T-leukemia cell lines (CCRF-CEM, HPB-ALL, JM and MOLT-4) by the phorbolester 12-0-tetradecanoylphorbol 13-acetate (TPA). The isoenzymes of carboxylic esterase, acid phosphatase, hexosaminidase and lactate dehydrogenase were separated by isoelectric focusing on horizontal thin-layer polyacrylamide gels and stained by histo-cytochemical methods. TPA inhibited the proliferative activity in all four cell lines and led to aggregation of cells seen as floating clusters. TPA induced an increase in number and staining intensity of isoenzymes of all four enzymes in the cell lines studied. This corresponds to an induced isoenzymatic maturation as the progressive increase in number and staining intensity of the isoenzymes parallels the differentiation along the T-cell pathway. However, regardless of the initial stage of arrested differentiation, the cell lines could be induced only to differentiate to a certain more mature stage, but could not be triggered to differentiate terminally with regard to expression of isoenzyme patterns.
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PMID:T-leukemia cell lines CCRF-CEM, HPB-ALL, JM and MOLT-4: changes in isoenzyme profiles during induction of differentiation. 349 47

Serum ferritin concentrations were determined in 142 untreated cases of acute leukaemia. No correlation between type of leukaemia as defined by morphology and immunology and the level of serum ferritin was found. Samples were also tested for lactate dehydrogenase (LDH), phosphohexose isomerase (PHI), B-glucuronidase (B-gluc), leucine aminopeptidase (LAP), and C-reactive protein (CRP) levels. Serum ferritin was significantly correlated with serum PHI, LAP, and LDH concentrations but not with leukaemic mass as assessed by total white blood cell count (WBC). Ferritin and CRP levels were also significantly correlated suggesting that ferritin may behave to some extent like an acute phase reactant in acute leukaemia.
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PMID:Serum enzyme and ferritin concentrations in acute leukaemia. 350 81

To identify adults with acute nonlymphocytic leukemia at risk for the development of central nervous system involvement, we performed periodic cerebrospinal fluid examinations on patients in remission. Among 58 consecutive patients monitored during first remission, central nervous system leukemia developed in nine (16 percent). Four patients, including one who was symptomatic, had central nervous system leukemia detected simultaneously with marrow relapse. Five additional patients were asymptomatic and continue to have bone marrow remission. Following central nervous system and systemic treatment, two of these five patients have never had relapse, and three had relapse in the bone marrow five, 10, and 21 months later. Factors at diagnosis associated with the subsequent development of central nervous system leukemia were elevated leukocyte count, serum lysozyme and lactate dehydrogenase, extramedullary infiltration including splenomegaly, and monocytic (FAB M4 or M5a) morphology. In six of 17 patients (35 percent) with monocytic morphology, central nervous system leukemia developed compared with only three of 41 patients (7 percent) with other subtypes (p = 0.02). Discriminant analysis identified leukocyte count, splenomegaly, and M4 or M5a morphology as the most important risk factors and led to a mathematical formula that correctly identified 90 percent of the patients. Although the risk of central nervous system leukemia in adults with acute nonlymphocytic leukemia is too low to justify routine prophylaxis, those patients recognized to be at a greater risk should receive prophylaxis or be monitored closely with periodic lumbar punctures.
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PMID:Central nervous system involvement in acute nonlymphocytic leukemia. A prospective study of adults in remission. 366 83

Cellular and humoral markers of malignancy play several roles at many levels in the evaluation and staging of children with cancer. Cytogenetic analysis of constitutional cells can be used to determine the genetic risk of developing certain cancers, such as retinoblastoma and Wilms' tumor in high-risk families. Urinary metabolites of neuroblastoma have been studied not only for accurate diagnostic ability in children with "small round cell" tumors, but as a screen for the presence of the tumor in large normal populations. Markers are valuable as prognostic factors at the time of cancer diagnosis; for example, the use of cell surface antigens and cytogenetics in leukemia phenotyping, leading to alterations in initial therapy. Once found at diagnosis, both specific and nonspecific markers can then be utilized to follow the regression and recurrence of a malignancy, such as serum ferritin in neuroblastoma or lactate dehydrogenase in non-Hodgkin's lymphoma. Presence of cell surface antigens to which monoclonal antibodies can be directed are becoming increasingly helpful in both tumor localization, such as in radioisotope scanning, and in therapeutic intervention, such as in purging autologous bone marrow of malignant cells prior to use as a rescue after massive cytoreduction. Finally, cellular markers have lead to a better understanding of the basic biology of particular neoplasms; for example, gene rearrangements in lymphoma, which will ultimately lead to better diagnostic and therapeutic ability.
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PMID:The use and significance of biologic markers in the evaluation and staging of a child with cancer. 371 38

Isoelectric focusing (IEF) in horizontal polyacrylamide gels has been used to separate lactate dehydrogenase (LDH) isoenzymes in 97 human permanent hematopoietic cell lines (85 leukemia-lymphoma cell lines and 12 'normal' B-lymphoblastoid cell lines). Maximally 8 LDH bands were seen; the electrophoretically detectable bands 4 and 5 could be separated by IEF into 2 and 3 isoenzymes, respectively. The LDH patterns have been found to vary both in number of isoenzymes and in relative intensity in different cell lines depending upon the stage at which arrest of differentiation occurred. These differences can be used to analyse and distinguish different cell lines. The method should provide a valuable supplement to the enzymatic phenotyping and complete characterization of fresh and cultured leukemias and for the monitoring of phenotypic changes occurring during induction of differentiation.
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PMID:Isoenzyme studies in human leukemia-lymphoma cell lines--IV. Lactate dehydrogenase. 387 28

Neoplastic thymocytes from rat thymic lymphoma-leukemias induced by the rat-adapted Gross leukemia virus (RAGV) were analyzed for a variety of differentiation markers. The neoplasms from individual rats all expressed the antigenic phenotype MP+, W3/13+, Thy-1+, RT-1+, RT-7+, W3/25-. However, approximately two-thirds of the neoplasms were positive for the OX 8 antigen, and one-third were negative. The OX 8- neoplasms only involved the thymus, whereas approximately 40% of the OX 8+ neoplasms involved the spleen as well as the thymus. Virtually all OX 8+ and OX 8- neoplastic cells contained terminal deoxynucleotidyl transferase (TdT), and both OX 8+ and OX 8- lymphomas expressed the lactate dehydrogenase (LDH)-5' isozyme and the primary, but not the secondary, ADA isozyme. This enzymatic phenotype is characteristic of thymocyte precursors, but not thymocytes. Our results therefore indicate that RAGV-induced lymphomas arise from transformed prethymic TdT+ cells which contain the LDH-5' and the primary ADA isozymes. These preleukemic cells presumably migrate to the thymus where they express the RT-7 pan-T-cell antigen and, in some instances, the OX 8 antigen during the development of overt leukemia. The OX 8+ neoplasms, being more differentiated than their OX 8- counterparts, then migrate to peripheral lymphoid tissues.
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PMID:Phenotypic heterogeneity of Gross virus-induced thymic lymphomas in the rat: cellular origins and migratory properties. 387

Profound changes in the level of certain dehydrogenase enzymes were observed in lymphoid tissues of rats involved by erythroblastic stem cell leukaemia. In lymphoid tissues free of leukaemic involvement, activity of malate dehydrogenase (MDH) always exceeded that of lactate dehydrogenase (LDH). In those which contained substantial infiltrates of leukaemic cells, activity of LDH was increased while MDH activity was reduced. In leukaemic spleen significant changes were observed in the molecular forms of LDH; the proportion of LDH-5 (muscle-type LDH) was greatly increased while the other molecular forms were reduced. The spleen of rats with leukaemia exhibited a marked increase in the normal level of aerobic and anaerobic glycolysis but the rate of respiration was unchanged.The terminal stages of stem cell leukaemia in the rat are characterized by wide-spread leukaemic infiltration of liver and other tissues. Lymph node involvement, however, was found to be selective. Coeliac lymph nodes greatly exceeded other lymph node groups in their incidence of leukaemic involvement. It is considered that the selective nature of lymph node involvement in stem cell leukaemia derives from topographical considerations.
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PMID:Leukaemia evoked with 7,8,12-trimethylbenz(a)anthracene in rat. 3. Changes in lymphoid tissues. 508 76

An early sign of erythroblastic leukemia in rat was nodule formation in the spleen. Hyperplastic foci of stem cells, indistinguishable histologically from leukemic stem cells, were found in the red pulp whereas the malpighian corpuscles were uninvolved. Anemia is a normal phenomenon in immature rats and the spleen of the prepubertal rat possesses considerable hemopoietic potential. Pulse-doses of 7, 8, 12-trimethylbenz(a)anthracene prevented the physiologic hematological development of maturing rats and was associated with subsequent development of leukemic stem cells in the red pulp of the spleen. Significant enzyme changes were observed in leukemic spleens. Compared with the spleens of normal littermates, the concentration of lactate dehydrogenase rose while that of malate dehydrogenase fell; the content of alkaline phosphatase rose whereas acid phosphatase fell. Increased alkaline phosphatase activity in leukemic spleen was attributed to nonleukemic foci of myelopoiesis.
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PMID:Leukemia evoked with 7,8,12-trimethylbenz(a)anthracene in rat. I. Changes in spleen and thymus. 528 70


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