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 relationship between cell features by light microscopy and therapeutic outcome of 72 patients with acute myeloblastic leukemia (FAB M1) were investigated. The patients were divided into two groups according to myeloperoxidase-(MPO) positive percentage of blast cells, namely a low (less than 50%) and high (greater than 50%) MPO group. No remarkable morphological difference of blast cells between these two groups was observed. The 38 patients with low MPO showed a significantly lower complete response rate (CR) (52.6%) than the 34 patients with high MPO (85.3%) (p = 0.003) that included 10 CAE-positive patients and 2 ANAE-positive CAE-negative patients. The low MPO group included 5 CAE-positive patients with granulocyte dysplasia and 7 additional patients with alpha naphthyl acetate esterase (ANAE) positivity who were chloroacetate esterase (CAE) negative. Low positivity of blast cells may be due to a defective enzyme expression in the former but also may be a reflection of 'monocytic' aberrant expression in the latter. The low MPO group in M1 with this heterogeneous population is less likely to achieve CR with chemotherapy, while the high MPO group with a higher CR rate suggests a more pure entity within the myeloblastic leukemias referred to as M1. After further refinement by eliminating 24 cases that were 'esterase positive' (ANAE and/or CAE), the results were still the same, suggesting that the more immature blast populations were in the low MPO group.
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PMID:Prognostic significance of myeloperoxidase positivity of blast cells in acute myeloblastic leukemia without maturation (FAB: M1): an ECOG study. 256 Jul 75

cDNA clones complementary to mRNA of cells from patients with chronic lymphocytic leukemia (CLL) were used to examine quantitative changes in the mRNA levels of specific genes in human leukemia leukocytes. Twenty one CLL-positive clones that did not hybridize with placental mRNA were studied. These clones were significantly represented in the mRNA from leukemic leukocytes and were not represent in the mRNA from normal leukocytes. There was high level of expression of 7-2D gene in CLL and B lymphoma cells. RNA hybridizing with clone 7-3G was comparatively highly abundant in CCRF-CEM and EB virus transformed lymphoid cell, while clone 6-1E was highly represented in the mRNAs of Molt 3 and CCRF-CEM cells. The expression of three clones (6-1E, 7-3G and 9-5C) selected from a CLL cDNA library was studied by nucleic acid hybridization in human promyelocytic leukemia cell (HL-60) treated with chemical inducers of cell differentiation. The differentiation of HL-60 cells into macrophage-like cells upon induction by 12-o-tetradecanoylphorbol-13-acetate (TPA) was accompanied by rapid induction of the expression of 6-1E and 7-3G genes. The levels of expression of the 9-5C gene were not altered during macrophage-monocytic or granulocytic differentiation of HL-60 cells. The expression of the 6-1E and/or 7-3G gene was induced by TPA in four of 6 samples derived from patients who achieved complete remission, but not in any of the acute nonlymphocytic leukemia samples from patients who failed to achieve complete remission. These findings suggest that expression of the 6-1E and 7-3G genes is related to macrophage-monocytic differentiation and that alterations of these gene expressions in fresh leukemic cells after one hour of TPA treatment are of prognostic significance in predicting the response to treatment. The primary structure of a cDNA of a gene (6-1E) selectively expressed in CLL was determined. A computer search in the nucleotide sequence data bank did not identify this gene as any other gene. The 677 nucleotide mRNA is composed of a 384 nucleotide pol A tail. Moreover, the sequences of the other cDNA clones (1-6G, 5-2C,5-5G, 6-1G, 7-3G, 7-4A, 8-6G, and 9-5C) are not present in those of the data base of GenBank recorded up to 1988.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Expression of selected genes and oncogenes in differentiated HL-60 cells and primary cells from human leukemias. 258 22

Dipeptidyl peptidase IV (DPP IV) is a specific enzyme for cells of T-lymphocytic lineage. It has been attempted to induce DPP IV activity in DPP IV negative T-lymphoid leukaemias by 12-o-tetradecanoylphrobol-13-acetate (TPA). Isolated cells from peripheral blood of 6 healthy blood donors and 22 patients with various types of leukaemia were cultivated in RPMI-1640 medium with 20% fetal calf serum alone (control) or supplemented with 20% human placenta conditioned medium (HPCM) or with 16 nmol/l TPA for 3 days. The percentage of DPP IV positive lymphocytes from blood donors remained unchanged in control and HPCM cultures, but decreased significantly in TPA cultures. Leukemic cells from three DPP IV positive cases of acute T-lymphoblastic leukaemia (T-ALL) reacted to the TPA treatment in a similar manner. Leukaemic cells of two DPP IV negative T-ALL cases remained negative in all three types of cultures, thus no induction of DPP IV activity was found. Other normal blood cells as well as leukaemic cells of 7 null-ALL, 1 preB-ALL, 3 B-CLL and 6 AML patients were DPP IV negative before and after cultivation in all types of culture. These findings showed that DPP IV is specifically expressed in cells of T-lymphocytic lineage even after short-term cultivation. HPCM was found to have no effect on DPP IV activity in T-lymphoid cells.
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PMID:Dipeptidyl peptidase IV activity in cells of T-lymphoid origin is decreased in cultures with 12-0-tetradecanoylphorbol-13-acetate (TPA). 289 91

In order to investigate the clinical significance of surface antigen analysis in acute myeloblastic leukemia (AML), the blasts from 196 patients with AML were analyzed prospectively with a panel of 16 monoclonal antibodies. The antibodies were selected to identify differentiation-associated antigens of either the myeloid lineage (MY9, PM-81, AML-2-23, MY7, MCS-1, MY8, Mo1, MY1, MY4, Mo2), T cell lineage (T101, T11), B cell lineage (B1, B4) or multiple lineages [J5 (CALLA), HLA-DR]. Independent morphological review and classification by French-American-British (FAB) criteria was performed in 161 of the 196 cases. One or more myeloid surface antigens were detected on the blasts of 195 cases, while B and T cell markers were detected on 0% to 2% of cases. When both blood and marrow samples were studied on the same patient, very few differences were noted between the antigenic profiles of the paired specimens. The frequency of expression of individual myeloid antigens ranged from 91% (PM-81) to 29% (Mo2). Expression of individual antigens was found to correlate significantly with several clinical parameters including FAB classification, cytochemical staining for alpha naphthyl acetate esterase, leukocyte count, and the presence of extramedullary disease at presentation. Two myeloid antigens (MY4 and MY7) predicted for a low rate of complete remission (CR) to standard induction chemotherapy. MY4+ cases (37% of the total population) had a CR rate of 53%, while M4- cases had a CR rate of 69% (P = .03). MY7+ cases (57% of the total population) had a CR rate of 55% while MY7- cases had a CR rate of 73% (P = .01). Neither MY4 nor MY7 antigen expression was correlated with patient age. Paired combinations of antigens were also examined. The [MY4- MY7-] phenotype was exhibited by 32% of all cases and was associated with an 82% CR rate while the CR rate of all other cases was 54% (P = .001). The expression of three antigens (HLA-DR, MY8, Mo1) was associated with a decreased continuous complete remission (P less than .05, median follow-up time of 19 months). Expression of MY8 antigen was also associated with decreased survival (P = .03). These results confirm earlier reports of antigenic heterogeneity in AML, and indicate that immunologically defined subgroups of AML patients which are of potential clinical significance can be identified.
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PMID:Use of surface marker analysis to predict outcome of adult acute myeloblastic leukemia. 294 31

A leukemic cell line (HL60) and acute myeloblastic leukemia (AML) cells from six patients were co-cultured with normal marrow cells to assess their effects on growth of normal CFU-GEMM. The effects of the following inducers: 12-0-tetradecanoyl-phorbol-13-acetate (TPA), retinoic acid (RA), dimethylsulphoxide (DMSO), 1-25 (OH) D3 (Vitamin D3) and PHA-LCM on both the HL60 and AML cells, were studied. Inhibition of growth of normal CFU-GEMM was observed in the co-cultures in the presence of 1 X 10(4) HL60 or AML leukemic cells/ml. This inhibition was reversed by pretreating the HL60 line with vitamin D3, TPA and RA. No effect on growth of CFU-GEMM was noted when DMSO and PHA-LCM were used. AML cells were morphologically induced to differentiate by TPA or RA in all six cases. In three cases, reversal of inhibition of growth of normal pluripotent hemopoietic progenitors occurred and in three the inhibition of growth persisted. Regulation of inhibition by different inducers did not seem to correlate in all cases with morphological differentiation.
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PMID:The effect of the leukemic cell line HL60 and acute myeloblastic leukemic cells before and after induction of differentiation on normal pluripotent hematopoietic progenitors (CFU-GEMM). 298 22

A cytochemical study using: Sudan black B; alpha-naphthyl acetate (ANAE) staining; estimation of alpha-naphthyl butyrate (ANBE) esterase activity; acid phosphatase activity; and 5' nucleotidase activity was carried out in 15 cases of megakaryoblastic leukaemia. These included cases of M7 acute myeloid leukaemia and blast crises of chronic granulocytic leukaemia. The megakaryoblastic nature of the blasts was first established using two monoclonal antibodies against platelet glycoproteins, and by estimating the platelet/peroxidase reaction at ultrastructural level. Our findings suggest that megakaryoblasts have a typical cytochemical profile comprising positive ANAE staining and acid phosphatase activity with a predominant localisation in the Golgi zone and negative or weak ANBE activity. A similar positive cytochemical pattern was also found in five cases of erythroleukaemia (M6). The specificity of the 5'nucleotidase activity for megakaryoblasts was not confirmed. In most cases of megakaryoblastic leukaemia there was no 5'nucleotidase activity only two cases showed positive reactions--reactions were positive in several cases of myeloblastic and lymphoblastic leukaemia. We suggest that cytochemical methods may be useful in diagnosing M6 and M7 acute leukaemia because less than 40% of leukaemic cells react with specific monoclonal antibodies.
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PMID:Cytochemical profile of megakaryoblastic leukaemia: a study with cytochemical methods, monoclonal antibodies, and ultrastructural cytochemistry. 303 65

In acute myeloid leukemia the leukemic cells are thought to be blocked in their normal differentiation. The stage of differentiation is the basis for the FAB classification. Induction of cell differentiation is a new and promising development in the treatment of some myeloproliferative diseases. The criteria for cell maturation and differentiation are almost all based on the morphology of the leukemic cells. In this study we tried to specify the maturation stage of the leukemic cells by quantitative enzyme analysis. In the HL60 (promyelocytic) cell line cells we determined the following enzymes: myeloperoxidase; alpha naphthyl acetate esterase; alpha naphthyl butyrate esterase and lactate dehydrogenase. The enzyme profiles obtained after culturing the cells in the presence of the differentiation inducing agents 1:25 dihydroxy vitamin D3 and DMSO were compared with several cytochemical and functional parameters. The results obtained in this study show that quantitative enzyme analysis is a useful tool in the study of myeloid or monocytic differentiation.
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PMID:Quantitative enzyme determination; a parameter for leukemic cell differentiation. 303 59

gamma-Interferon (IFN-gamma) has previously been found to induce monocytic differentiation in established leukemic cell lines, such as HL-60 and U937. The aim of the present study was to evaluate the differentiative effect of highly purified recombinant (r)IFN-gamma on fresh bone marrow cells from patients with acute nonlymphocytic leukemia (n = 11) or myelodysplastic syndromes (n = 3). Blast cells were cultured in suspension in the presence or absence of rIFN-gamma (10-10(3) U/ml). While 6 out of 14 cases were unresponsive to rIFN-gamma in vitro, the remaining 8 patients showed a significant increase (0.05 greater than p greater than 0.001) in the percentage of cells expressing C3bi receptors, detected by OKM1 (median value in control cell, 9.5; median value in rIFN-gamma-treated cells, 31) and Mo1 (8.5 vs. 36), and in the percentage of cells expressing the monocytic antigens detected by Mo2 (8 vs. 28) and MY4 (6.5 vs. 32.5). In the responsive patients morphologic changes consistent with monocytic maturation, as well as a strong increase of alpha-naphthyl acetate esterase activity and of nitroblue tetrazolium reducing capability were observed upon culture with rIFN-gamma. We conclude that (a) rIFN-gamma may induce in vitro monocytic differentiation of blasts from acute nonlymphocytic leukemia and myelodysplastic syndrome patients, and that (b) this agent should be investigated for its capacity to be active in vivo.
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PMID:Recombinant gamma-interferon induces in vitro monocytic differentiation of blast cells from patients with acute nonlymphocytic leukemia and myelodysplastic syndromes. 312 8

Phorbol ester, 12-0-Tetradecanoyl-13-Phorbol-Acetate (TPA), induces a terminal macrophage-like differentiation of cells from human acute myelogenous leukemia cell lines. We report here that blastoid cells obtained from acute nonlymphocytic leukemia (M1-M2) undergo differentiation-related changes characteristic of macrophage lineage after exposure to TPA. Blast cells from a patient with ANLL-M1-M2 underwent morphological, functional and histochemical changes after treatment with 1 x 10(-7) and 1 x 10(-8) M TPA. The changes included adhesion to the plastic substrate, 2-4 fold increase in the number of NBT positive cells and an increase in the number of alpha-naphthyl-acetate esterase (alpha-NAE) positive cells. These differentiation changes after treatment with TPA were followed by decrease in proliferative index and G1 cells containing high RNA as estimated by flow cytometry. Of the thirteen cases of undifferentiated or unclassified leukemias studied, two failed to respond to TPA. These data suggest that leukemic blasts retain their ability to express a variety of differentiated functions on induction by TPA. Our data gives evidence suggesting that the "switch" into the differentiation pathways occurred after inhibition of proliferation and reduction in the percentage of G1 high RNA containing cells.
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PMID:Terminal differentiation of human leukemic blasts in response to 12-0-tetradecanoyl-13-phorbol acetate (TPA). 321 70

A new cytokine has been recognized in the conditioned media (CM) of freshly isolated acute myelocytic leukemia cells, cultured with 12-0-tetradecanayl phorbol acetate (TPA) 10(-8)M. The fraction with 70,000 MW was separated from CM by ammonium sulfate precipitation, ion-exchange cation and anion chromatography, and Sephadex G-200 gel filtration. It was a fibroblast growth inhibitor (FGI). This substance stopped fetal and skin (MALME 3 line) fibroblast propagation. The cytostatic effect was reversible on removal of FGI. At the same time, FGI did not inhibit macrophage proliferation. The fraction stimulated formation of monocytic and granulocytic colonies altered the phenotype of human U-2 osteosarcoma cells grown from epithelial-like to fibroblast-like cells, and stimulated differentiation of leukemic cells along the macrophage path. Some cells of promyelocytic leukemia line HL-60, grown in the presence of FGI, were stimulated to differentiate and some underwent lysis. The response to FGI of cells from different patients varied.
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PMID:Fibroblast growth inhibitor. 322 59


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