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)

Since the last workshop on human leukocyte differentiation antigens, there are 14 well defined cluster-designated (CD) antigens which characterize myelomonocytic cells. Of these, 5 are potentially useful for myeloid leukemia typing (i.e. CD13, CD14, CD15, CD33, CD36) because they are cell lineage-specific and also expressed on immature cells. However, the reactivity of monoclonal anti-CD antibodies, directed against these antigens, with myeloblastic leukemia cells was found to be quite low. We produced monoclonal antibodies against myeloperoxidase. These antibodies react also with promyeloperoxidase, synthesized in HL-60 cell line cells. Monoclonal antimyeloperoxidase was found to be the most sensitive reagent to diagnose acute myeloid leukemia, even more sensitive than cytochemical stains (Sudan black, myeloperoxidase).
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PMID:Characterization of myeloid leukemia by monoclonal antibodies, with an emphasis on antibodies against myeloperoxidase. 282 87

For 147 patients with myeloproliferative diseases, a study was made of the expression of Fc-receptors to immunoglobulins IgC, IgA, and that of FcH-receptor and receptors to C3-components of the complement in peripheral blood neutrophils. The data obtained show the lower level of neutrophils having membrane receptors in patients with acute myeloblastic leukemia and chronic granulocytic leukemia at the stage of blast transformation. A decrease in expression of membrane receptors of neutrophils was shown in patients with chronic granulocytic leukemia and benign subleukemic myelosis. The finding of a higher level of neutrophils having surface receptors revealed in patients with real polycythemia is close to the data obtained in the study of expression of membrane receptors in patients with chronic myeloproliferative diseases and healthy persons.
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PMID:[Expression of the surface membrane receptors of neutrophils in myeloproliferative diseases]. 294 11

We examined synthesis of the cellular phosphoprotein p53 in fresh bone marrow or peripheral blood cells from normal donors and from patients with leukemia, preleukemia, or other hematopoietic disorders. Lysates of cells labeled with [35S]methionine were immunoprecipitated with monoclonal antibodies to p53, and the immunoprecipitates were analyzed by NaDodSO4/polyacrylamide gel electrophoresis and autoradiography. Bone marrow or peripheral blood cells from 8 of 33 patients with hematopoietic disorders showed increased p53, seven of the eight occurring in cells of patients with preleukemia or acute myelogenous leukemia. Increased p53 synthesis was not associated with p53 gene amplification, as shown by Southern blot analysis. Synthesis of p53 was not increased in any of nine normal human bone marrow samples or eight normal human peripheral blood granulocyte, macrophage, and lymphocyte samples. The hematopoietic cells of patients in remission or with chronic forms of leukemia did not generally synthesize elevated levels of p53. In addition, we found negligible p53 mRNA and protein expression in a variety of human myeloid leukemia lines blocked at different stages of differentiation. Southern blot analysis showed that, except for the HL-60 cells, the p53 gene of the myeloid cell lines was intact. In view of recent evidence implicating p53 in transformation of cultured cells, our results using fresh leukemia cells suggest that p53 may contribute to the phenotype of certain leukemias in vivo.
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PMID:Increased expression of p53 protein in human leukemia cells. 301 45

The clonogenic growth of myeloid leukemia cell lines was inhibited by recombinant tumor necrosis factor (rTNF) at 1-15 pM concentration. However, wild type (promyelocytic) HL-60 cells were highly resistant to growth inhibition, but responded with differentiation into monocyte-like cells at 100 pM rTNF. The clonogenic growth of fresh acute myeloid leukemia cells was inhibited by 50% at approximately 15 pM rTNF. The growth of normal granulocyte-macrophage progenitors (CFU-GM) was also inhibited (by 50 pM rTNF), as was the growth of erythroid progenitors (BFU-E) (by 150 pM rTNF). A synergistic antiproliferative effect was demonstrated between rTNF and recombinant interferon-gamma. Use of radioiodinated rTNF enabled us to detect 1,500-2,100 binding sites on myeloid cell lines at 4 degrees C with Kd of approximately 300 pM. At 37 degrees C, the transfer of bound ligand to lysosomes was followed by degradation, inhibited by NH4+. No correlation was observed between the number of binding sites or affinity at 4 degrees C and antiproliferative response to the addition of rTNF.
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PMID:Effects of recombinant tumor necrosis factor on proliferation and differentiation of leukemic and normal hemopoietic cells in vitro. Relationship to cell surface receptor. 302 50

Recent advances in the modulation of cell kinetics with growth factors suggest that the effect of cycle-specific cytostatic drugs can be enhanced by combination with such factors. The truth of this hypothesis was investigated by studying the effect of phytohemagglutinin and/or interleukin 2 on the sensitivity to methotrexate (MTX) of normal T lymphocytes and of lymphoblasts of a patient with acute T-cell lymphoid leukemia. In both cases, inhibition of proliferation by MTX was increased from less than 30% in resting cells or those suboptimally stimulated, in the case of leukemic blasts, to 68-83% in maximally stimulated cells. Similar results were observed when the AML 193 human myeloid leukemia line was stimulated with human recombinant granulocyte macrophage colony stimulation factor (GM-CSF). Under basal proliferation conditions, the addition of 1 microgram/ml and 10 micrograms/ml MTX was followed by 48% and 72% inhibition respectively. When 1 ng/ml GM-CSF (40 I.U./ml) was present, these figures rose to 89% and 91%. It is thus clear that growth factor-induced cell proliferation increases sensitivity to cycle-specific cytostatic agents. There is thus a biological premise for new perspectives in antineoplastic therapy.
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PMID:Enhancement of methotrexate cytotoxicity by modulation of proliferative activity in normal and neoplastic T lymphocytes and in a myeloid leukemia cell line. 306 71

The influences of human tumor necrosis factor (TNF) (LuKII), recombinant human TNF-alpha, natural human interferon-gamma (HuIFN-gamma), recombinant HuIFN-gamma, and natural HuIFN-alpha were evaluated alone or in combination for their effects in vitro on colony formation by human bone marrow granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells incubated at 5% CO2 in lowered (5%) O2 tension. TNF (LuKII) and recombinant TNF-alpha caused a similar dose-dependent inhibition of colony formation from CFU-GM, BFU-E, and CFU-GEMM. Day 7 CFU-GM colonies were more sensitive than both day 14 CFU-GM colonies and day 7 CFU-GM clusters to inhibition by TNF. BFU-E colonies and CFU-GEMM colonies were least sensitive to inhibition with TNF. The suppressive effects of TNF (LuKII) and recombinant TNF-alpha were inactivated respectively with hetero-anti-human TNF (LuKII) and monoclonal anti-recombinant human TNF-alpha. The hetero-anti-TNF (LuKII) did not inactivate the suppressive effects of TNF-alpha and the monoclonal anti-recombinant TNF-alpha did not inactivate TNF (LuKII). The suppressive effects of TNF did not appear to be mediated via endogenous T lymphocytes and/or monocytes in the bone marrow preparation, and a pulse exposure of marrow cells with TNF for 60 min resulted in maximal or near maximal inhibition when compared with cells left with TNF for the full culture incubation period. A degree of species specificity was noted in that human TNF were more active against human marrow CFU-GM colonies than against mouse marrow CFU-GM colonies. Samples of bone marrow from patients with non-remission myeloid leukemia were set up in the CFU-GM assay and formed the characteristic abnormal growth pattern of large numbers of small sized clusters. These cluster-forming cells were more sensitive to inhibition by TNF than were the CFU-GM colonies and clusters grown from the bone marrow of normal donors. The sensitivity to TNF of colony formation by CFU-GM of patients with acute myelogenous leukemia in partial or complete remission was comparable with that of normal donors. When combinations of TNF and HuIFN were evaluated together, it was noted that TNF (LuKII) or recombinant TNF synergized with natural or recombinant HuIFN-gamma, but not with HuIFN-alpha, to suppress colony formation of CFU-GM, BFU-E, and CFU-GEMM from bone marrow of normal donors at concentrations that had no suppressive effects when molecules were used alone.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The suppressive influences of human tumor necrosis factors on bone marrow hematopoietic progenitor cells from normal donors and patients with leukemia: synergism of tumor necrosis factor and interferon-gamma. 308 33

The accumulation of cytosine arabinoside-5'-triphosphate (ara-CTP), the activities of nucleotide-metabolizing enzymes and the nucleoside transport capacity were examined in eleven human leukemic cell lines differing in phenotype. The highest amount of ara-CTP was accumulated in T-acute lymphoblastic leukemia cells (T-ALL), followed by myeloid leukemia cell lines (AML), and the least accumulation was observed in common acute lymphoblastic leukemia (c-ALL) and B-acute lymphoblastic leukemia cells (B-ALL). The levels of enzymes involved in ara-C metabolism (deoxycytidine kinase, pyrimidine monophosphate kinase and deoxycytidylate deaminase) did not correlate with ara-CTP accumulation. The sensitivity of the leukemic cell lines to ara-C, which was measured in terms of decrease of clonogenic survival, correlated with the amount of ara-CTP formed. Moreover, the nucleoside transport capacity, estimated from the binding of the radiolabeled nucleoside analogue, [3H]nitrobenzylthioinosine, showed a good correlation with ara-CTP accumulation. The mean numbers of nucleoside-binding sites in T-ALL cells were significantly greater than in B-ALL cells. We conclude that the cellular nucleoside transport capacity is the most important factor for the formation and accumulation of ara-CTP in the cells.
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PMID:Formation of cytosine arabinoside-5'-triphosphate in cultured human leukemic cell lines correlates with nucleoside transport capacity. 311 33

The mediastinum is seldom involved by granulocytic sarcoma and superior vena cava (SVC) obstruction is an even rarer presentation. Some radiologists advocate to treat SVC obstruction as a semimedical emergency regardless of the underlying pathology. This policy has been criticized. We describe a patient with severe SVC obstruction preceding the development of frank acute myeloblastic leukemia and granulocytic sarcoma in breasts. Review of the literature yields 11 patients with prominent mediastinal granulocytic sarcoma complicating myeloid leukemia; 3 of them presented with superior vena cava syndrome.
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PMID:Superior vena cava syndrome: a rare presenting feature of acute myeloid leukemia. 313 4

The effect of recombinant human tumor necrosis factor alpha (rTNF-alpha) on human myelogenous leukemia clonogenic cells growing either in semisolid media or in suspension cultures was studied and compared with the effect on normal granulocyte-macrophage progenitors (GM-CFC). Exposure of cells to a range of rTNF-alpha doses including pharmacologically achievable plasma concentrations revealed a large heterogeneity in the response of leukemic clonogenic growth to rTNF-alpha. Only one of 13 specimens was highly resistant to rTNF-alpha. Eight of ten leukemic samples were significantly more sensitive than were normal GM-CFC, particularly within the in vivo achievable dose range (1 x 10(0) to 1 x 10(2) ng/mL). No significantly increased inhibition of either normal or leukemic clonogenic growth could be achieved by increasing the rTNF-alpha concentration above 250 ng/mL. Proliferation of leukemic clonogenic cells (L-CFC) was studied in suspension cultures. In five cases the clonogenic cells were significantly inhibited by rTNF-alpha while in one case no inhibition was observed. The inhibition of L-CFC growth by rTNF-alpha was dose dependent between 1 x 10(0) and 1 x 10(2) ng/mL. In suspension cultures, the TNF effect on L-CFC was a function of time of exposure, particularly with low concentrations of TNF. A remarkably higher inhibition of L-CFC as compared with the total leukemic population was observed in suspension cultures. Stimulation of L-CFC growth by rTNF-alpha was not observed. Normal GM-CFC were inhibited by alpha and gamma interferons (INF-alpha, -gamma) in a dose-related manner, with higher sensitivity of colonies than clusters. The response of GM-CFC to combination of recombinant IFNs and TNF was influenced by the size of clones scored and the source of colony-stimulating activity. The response of L-CFC to recombinant IFN-alpha and/or -gamma was highly variable, and sensitivity to one of the lymphokines did not predict for sensitivity to another. The response of L-CFC to combinations of rTNF-alpha and either IFN-alpha or IFN-gamma was complex, varying from synergistic to additive and indifferent. In three of six specimens, IFN-gamma acted antagonistically with rTNF-alpha, a phenomenon not observed with IFN-alpha. These observations suggest that the action of rTNF-alpha in acute myelogenous leukemia could be exploited therapeutically and the dose-time-response relationship should be considered in designing treatment schedules.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Antileukemic effect of recombinant tumor necrosis factor alpha in vitro and its modulation by alpha and gamma interferons. 313 64

We examined the capacities of sera from patients with myeloid leukemia to induce differentiation in mouse myeloid leukemic M1 cells. Higher differentiation-inducing activity (D-activity) was detected in sera of patients with chronic myelomonocytic leukemia or chronic myeloid leukemia (CML) than in sera of patients with acute myeloid leukemia and normal volunteers. The D-activity in the sera was lost on heating the sera at 56 degrees for 30 min. The major peak of D-activity on Sephadex G-200 gel filtration had an apparent molecular weight of 160,000. The origin of the D-activity in sera of patients with CML was studied by culturing fractions of peripheral blood cells of patients with D-activity for 3 days and then measuring the ability of the conditioned medium (CM) to induce differentiation of M1 cells. The cells in the myeloblast and promyelocyte fraction differentiated spontaneously into macrophage-like cells during culture for 3 days and the cells in the late granulopoietic cell fraction differentiated into neutrophil-like cells. Higher D-activity was present in CM of cells in the myeloblast and promyelocyte fraction than in CMs of late granulopoietic cell fractions. These results suggest that human leukemic cells produce D-activity for M1 cells during their differentiation into macrophage-like cells.
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PMID:Induction of differentiation of mouse myeloid leukemia M1 cells by serum of patients with chronic myeloid leukemia. 314 2


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