Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023467 (acute myeloid leukemia)
 35,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The alpha naphthyl acetate esterase (ANAE) cytochemical staining patterns were examined in 40 cases of acute myeloblastic leukaemia (AML: FAB groups M1 and M2) classified by morphological and immunological criteria. The blast cells in most cases (62%) were ANAE-negative with the remainder showing diffuse, granular or focal reactions of varying intensity. The nature of cytoplasmic ANAE enzymes was further characterised in 20 cases by isoelectrophoretic analysis of ANAE isoenzymes. The results suggest that the presence of significant cytoplasmic ANAE reactivity in leukaemic myeloblasts is not due to the presence of monocyte-associated isoenzymes, in otherwise well-defined myeloblasts, but may reflect abnormally increased synthesis or atypical localisation of normally-occurring ANAE isoenzymes. In particular, the results of this study indicate the lack of discriminatory value of ANAE cytochemistry in the differentiation of AML from other acute leukaemias of non-monocytic type.
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PMID:Cytochemical and electrophoretic characterisation of alpha naphthyl acetate esterases (ANAE) in acute myeloblastic leukaemia. 659 4

The effect of the plant diterpenes, phorbol derivatives and mezerein, on differentiation of various human myeloid leukemic cells to macrophages was determined. The results indicate that, within the group of phorbol esters tested, a correlation exists between the potency of the compounds as inducers of differentiation and their reported potency as tumor promoters. However, mezerein and 12-O-retinoylphorbol 13-acetate, which promote tumors only weakly or not at all, were found to be efficient inducers. The efficiency of all the active phorbol derivatives, including the weak inducers, also known to be weak promoters, could be potentiated by pretreatment of the cells with retinoids, compounds which have been reported to inhibit tumor promotion. Similar results were obtained in 3 different established cell lines, as well as in short-term cultures of cells obtained from patients with acute myeloid leukemia. The results suggest that the activities of the diterpenes as tumor promoters and inducers of differentiation are not necessarily linked. Moreover, certain conditions which are unfavorable for tumor promotion may not affect or even potentiate induction of differentiation.
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PMID:Differentiation of human myeloid leukemic cells by phorbol esters: correlation with tumor promotion. 659 8

Various human and mouse myeloid leukemia cell lines can differentiate to mature myeloid or monocytoid cells in response to different agents. The myeloblastic leukemia of the RFM/Un mouse (the RF.AML line) was studied here to determine its ability to differentiate after in vitro and in vivo treatment. The RF.AML cells were passed in vivo by i.v. or i.p. injection of freshly harvested leukemic spleen cells or in vitro-passaged leukemia cells. The cells proliferated in the spleen and peritoneal cavity. The RF.AML cells had the appearance of myeloblasts or myelomonoblasts on Wright's stain, had slight positivity for peroxidase, and lacked staining for nonspecific esterase. The cells grew in suspension in vitro with a doubling time of 48 hr. Various phorbol diester tumor promotors inhibited proliferation and incorporation of thymidine into the RF.AML cells. Phorbol myristate acetate (10 to 100 nM) caused the cells to adhere to plastic, and enhanced the phagocytic ability of the cells for Candida albicans. The RF.AML cells had specific receptors for phorbol dibutyrate, binding 0.37 +/- 0.03 (S.E.) pmol of [3H]phorbol dibutyrate/10(6) cells after a 2-hr incubation at 4 degrees with 50 nM [3H]phorbol dibutyrate. Thirty-three to 300 nM dexamethasone caused 19 to 37% of the cells to become nonspecific esterase positive and enhanced their phagocytosis of C. albicans. Likewise, 0.5 or 1.0 microM 13-cis-retinoic acid, or 0.6 or 1.2% dimethyl sulfoxide enhanced the phagocytic ability of the RF.AML cells but had no effect on the adherence, proliferation, or nonspecific esterase activity. None of the treatments induced lysozyme activity in the cells or rendered the RF.AML cells able to produce H2O2 in response to phorbol myristate acetate treatment in vitro. In vivo treatment of mice with RF.AML present with phorbol myristate acetate or dexamethasone did not induce differentiation of the RF.AML cells or alter the survival of the animals. Thus, although the RF.AML cells differentiate in vitro in response to various agents, in vivo differentiation was not seen in this model.
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PMID:Comparison of in vitro and in vivo differentiation of myeloblastic leukemia of the RFM/Un mouse. 659 93

A human lymphoblastoid cell line, SCC-1, was established from the bone marrow of a patient with acute nonlymphocytic leukemia. 12-O-Tetradecanoylphorbol-13-acetate (TPA) enhanced cell proliferation of SCC-1 cells in suspension culture. A positive correlation was found between the tumor-promoting activities of several plant diterpenes and their enhancing effects on the growth of SCC-1 cells. Various compounds that inhibit tumor promotion were tested for their capacity to inhibit cell proliferation at a physiological concentration. These compounds were not cytotoxic but cytostatic even at high concentration.
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PMID:Stimulation of cell proliferation by tumor-promoting phorbol esters and inhibition by some inhibitors of tumor promotion in suspension cultures of a human lymphoblastoid cell line. 660 57

The human HL-60 cell line derived from acute promyelocytic leukemia, consisting of promyelocytic type of cells, was able to differentiate into adherent cells with monocytemacrophage features by the treatment with 12-0-tetradecanoyl phorbol-13-acetate (TPA). Cell surface antigens of HL-60 cells before and after TPA treatment were studied with monoclonal antibodies and four hybridoma clones producing IgM antibodies were established. Two antibodies (HL-21 and HL-47) reacted only with the immunizing TPA-treated HL-60 cells, and HL-1 antibody produced against untreated cells was reactive with both TPA-treated and untreated cells, but HL-5 antibody reacted predominantly with the immunizing untreated cells. Serological reactivity against various types of normal hematopoietic cells and acute leukemias (diagnosed by the French-American-British classification) was studied by immune adherence assay and immuno-electron microscopy. HL-21 antibody was reactive with monocytes and most cases of M4 and M5 types of acute non-lymphocytic leukemia cells. HL-47 antibody did not react with the cells of myelocyte-monocyte lineage or mature lymphocytes, but it did react with one-third of acute lymphocytic leukemia (L1 and L2) cases. Since all HL-47+ cases were included in the group of common ALL antigen positive cases, it was estimated that HL-47 is a differentiation antigen present on lymphocyte precursors, from which null-cell type acute lymphocytic leukemia cells generally originate. HL-1 antibody reacted with the cells of myelocyte-monocyte lineage as well as those of most acute non-lymphocytic leukemias. HL-5 antibody reacted with granulocytes and M2 type of acute myelocytic leukemia cases, and also with M5 type of acute monocytic leukemia cases. Serological studies of these antibodies revealed that TPA can induce to differentiate HL-60 cells not only into HL-21+ macrophage-like cells, but also into HL-47+ lymphoid stem cells. In addition, these antibodies were demonstrated to be very valuable for differential diagnosis of acute leukemias.
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PMID:Serological analysis of cell surface antigens of HL-60 cells before and after treatment with a phorbol ester tumor promoter. 660 2

Myeloid leukemic cells can be induced to differentiate by various compounds, suggesting the possibility of controlling leukemia through induced differentiation. For this to be feasible, the growth of leukemic progenitor cells should be inhibited by these compounds, with the inhibition preferentially affecting leukemic over normal hemopoietic progenitor cells. 12-O-Tetradecanoylphorbol-13-acetate (TPA) was chosen as a differentiation inducer and was studied for its effect on the growth of leukemic colony-forming cells (L-CFU) in ten patients with acute nonlymphocytic leukemia in comparison with normal myeloid colony-forming cells (CFU-C). Growth inhibition of both L-CFU and CFU-C was observed with TPA concentrations as low as 10(-10) M. With increasing concentrations of TPA, survival of L-CFU tended to decline more precipitously than that of CFU-C. In eight of ten patients, inhibition of L-CFU was significantly greater (P less than 0.01) than CFU-C with TPA concentrations of 10(-9) M or higher. This study indicates that a compound capable of inducing differentiation of leukemic cells can inhibit growth of leukemic progenitor cells and that this growth inhibition applies preferentially to leukemic cells as compared with normal hemopoietic cells.
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PMID:Preferential growth inhibition of human leukemic versus normal myeloid colony-forming cells by 12-O-tetradecanoylphorbol-13-acetate. 672 21

Leukemic cells from patients with acute myeloid leukemia underwent morphological, functional, and histochemical changes within 24-48 hr after treatment with 1.6 x 10-18 M 12-0-tetradecanoylphorbol-13-acetate (TPA). The changes included adhesion to the plastic substrate, a 4-6-fold increase in the number of phagocytic cells, and an increase in the number of alpha-naphthyl-acetate esterase (alpha-NAE) positive cells. In contrast, TPA treatment of cells from patients with acute lymphoblastic leukemia caused some aggregation of cells in suspension, but no changes in adhesion, phagocytosis, or alpha-NAE. Of the four cases of undifferentiated or unclassified leukemias studied, two failed to respond to TPA, one responded with a myeloid (adhesion) pattern, and one with a lymphoid (aggregation) pattern. These data suggest that leukemic myeloblasts retain the ability to express a variety of differentiated functions, and in some cases, it may be possible to use TPA as a tool to test the differentiative potential of undifferentiated human leukemias.
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PMID:Differentiation of human leukemias in response to 12-0-tetradecanoylphorbol-13-acetate in vitro. 692 89

The HL-60 cell line, derived from a patient with acute promyelocytic leukemia, proliferates continuously in suspension culture and consists predominantly (greater than 90%) of promyelocytes. These cells can be induced to differentiate to morphologically and functionally mature granulocytes by incubation with a wide variety of compounds, including butyrate and hypoxanthine and polar planar compounds such as dimethyl sulfoxide and hexamethylene bisacetamide. We have now found that retinoic acid (all-trans-retinoic acid) induces differentiation (as measured morphologically and by the ability to reduce nitroblue tetrazolium) of HL-60 at concentrations as low as 1 nM. Maximal differentiation (approximately 90%) occurs at 1 micro M, a concentration 1/500th to 1/160,000th the concentrations of butyrate (0.5 mM) and dimethyl sulfoxide (160 mM) that promote a similar increase in differentiation. Continuous exposure to retinoic acid is necessary for optimal differentiation, with the percentage of mature cells in the culture directly related to the length of time of exposure to retinoic acid. Retinoic acid and 13-cis-retinoic acid are equally effective in inducing differentiation of HL-60. Retinol (vitamin A), retinal, and retinyl acetate are approximately 1/1000th less potent. This study suggests that retinoids could provide a therapeutic tool in the treatment of acute myeloid leukemia, a disease that has been looked upon as primarily involving a block in myeloid differentiation, and indicates that retinoids, in addition to their well-characterized involvement in epithelial cell differentiation, may also be involved in the differentiation of certain hematopoietic cells.
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PMID:Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid. 693 Jun 76

AML blast cell progenitors form colonies in culture when stimulated by a media conditioned by leukocytes in th presence of PHA. Two cellular processes occur during colony formation: self renewal generates new progenitors, while others undergo a change that leads to decreased proliferative potential. We tested the effect of the potent tumor promotor, 12-0-tetradecanoyl phorbol acetate (TPA) on these events. TPA was found to be toxic to blast cell colony formation; doses in excess of 1 ng per ml usually abolished it. At doses lower than this, self renewal, as determined by replating either individual or pooled colonies, was increased. At proliferation inhibiting TPA doses, surviving cells showed a spindle morphology, and had increased ANA esterase activity. We interpret the data to mean that TPA decreases blast cell maturation at low doses and may increase it at high doses.
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PMID:Dose-dependent effects of a tumor promotor on blast cell progenitors in human myeloblastic leukemia. 693 36

Twelve-O-tetradecanoyl phorbol-13-acetate (TPA) and other tumour promoter plant diterpenes transformed myeloid cells from peripheral blood, bone marrow and spleen from patients with chronic and acute myeloid leukaemia and acute myelomonocytic leukaemia into macrophage-like cells. This transformation resulted in cessation of cell multiplication, adherence of the cells to the surface of the culture dish, and acquisition of phagocytic activity, Fc receptors and enzymatic content characteristic of the monocyte-macrophage pathway of differentiation. The fact that tumour promoters induce differentiation in human myeloid leukaemia cells and not in similar cells from non-leukaemic conditions suggest their possible application in diagnosis and chemotherapy.
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PMID:Tumour promoters induce macrophage differentiation in human myeloid cells from patients with acute and chronic myelogenous leukaemia. 693 14


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