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

The growth of the human leukemia cell line AML-193 in a serum-free medium is strictly dependent on the presence of the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), which is one of the major regulators of the myelomonocytic lineage. At present, little is known about the mechanisms by which this growth factor transduces the signal intracellularly. The results of this study demonstrate that GM-CSF needs the operation of a Na+/H+ exchanger, which is located in the plasma membrane of almost every vertebrate cell. In fact, the GM-CSF-dependent proliferation of AML-193 cells is strongly reduced in the presence of the amiloride analog EIPA, a specific inhibitor of the Na+/H+ exchanger. When acidified, AML-193 cells are able to recover the original pHi in a Na(+)-dependent and EIPA-inhibitable way; this demonstrates for the first time the presence of the Na+/H+ exchanger in these cells. Finally, GM-CSF, at doses superimposable to those needed for triggering proliferation, induces in AML-193 cells a sustained alkalinization, which is dependent on a operating Na+/H+ exchange, as it is inhibited by EIPA. These results suggest that GM-CSF, like other growth factors in other cell systems, exerts its mitogenic activity in AML-193 cells by inducing a Na+/H+ exchanger-mediated rise in pHi.
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PMID:Role of Na+/H+ exchange in the granulocyte-macrophage colony-stimulating factor-dependent growth of a leukemic cell line. 215 71

We performed analyses of electrolytes, amino acids, albumin, alpha 2-macroglobulin, gamma-globulin and LDH in the lumbar cerebrospinal fluid of children undergoing treatment for acute lymphoblastic leukemia, non-Hodgkin-lymphoma or acute myeloid leukemia. At the time of diagnosis signs of a disturbance of the blood-brain barrier were found in some patients. During induction treatment with L-asparaginase a rise of glutamic acid and a decrease of glutamine occurred. This finding correlated with slowing of the EEG. Treatment with vincristine was associated with a slight drop of sodium and chloride concentration in serum, but not in the cerebrospinal fluid. Central nervous system prophylaxis with cranial irradiation, and to a lesser degree with intravenous medium-dose methotrexate, gave rise to a further deterioration of the blood-brain barrier function as indicated by an increase in albumin, alpha 2-macroglobulin and LDH levels. During radiotherapy the concentration of several amino acids rose, probably due to a disturbance of active carrier mechanisms. Patients with elevated albumin at the end of radiotherapy more often suffered an early leukemia relapse while still on treatment. No other clinical or electroencephalographic correlations of altered barrier function could be found.
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PMID:Electrolytes, amino acids and proteins in lumbar CSF during the treatment of acute leukemia in childhood. 233 48

All-trans-retinoic acid (RA), sodium n-butyrate (NaB), hexamethylene bisacetamide (HMBA), and dimethyl sulfoxide (DMSO) induce differentiation of the human acute myeloid leukemia cell line HL60. In the clinic, RA, NaB, or HMBA induce complete or partial remissions. However, the achievement and maintenance of effective plasma concentrations and toxicity have been problems. These difficulties led us to study the interaction of RA with these inducers. We found that combinations of RA with either NaB, HMBA, or DMSO synergistically induced terminal differentiation of HL60. A measure of the effectiveness of these combinations was that the doses of NaB, HMBA, and DMSO required alone to induce half-maximal differentiation were decreased about 4-fold in combination with normal plasma concentrations of about 30 nM RA. RA or NaB alone did not enhance the growth of HL60 cells. In contrast, HMBA or DMSO alone increased growth of HL60 cells even at concentrations that did not induce differentiation. The addition of RA reduced the promotion of growth and increased the extent of terminal differentiation seen with HMBA and DMSO alone. These data suggest that treatment of some malignancies with combinations of RA with HMBA or NaB may maintain differentiation-inducing effects and decrease the problems associated with the achievement and maintenance of effective plasma concentrations as single agents.
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PMID:Combinations of retinoic acid with either sodium butyrate, dimethyl sulfoxide, or hexamethylene bisacetamide synergistically induce differentiation of the human myeloid leukemia cell line HL60. 240 Sep 89

A murine monoclonal IgM erythrocyte antibody appeared to have anti-P (anti-globoside) specificity. The antibody was a relatively weak cold agglutinin, but a strong haemolysin and its reactivity with red cells was markedly enhanced by enzyme treatment. This antibody was used to study the cell and tissue distribution of globoside. Globoside was not only detectable on red cells and erythroblasts, but also on endothelial cells and on subsets of platelets, megakaryocytes and fibroblasts. It was not detectable on granulocytes, monocytes and most peripheral blood lymphocytes. Neither was it present on erythroblast precursors (CFU-E, BFU-E), pro-erythroblasts or on the cells of the pro-erythroblastic cell lines K562 and HEL. However, K562 cells expressed globoside when induced to mature into erythroblasts by sodium butyrate. Cells of patients with various leukaemias were also tested. A significant number of positively reacting cells was frequently (six out of 18) seen in cases with a CML blast crisis (CML-BC) and rarely in AML (four out of 37 cases). In CML-BC the P-positive cells were probably erythroblasts and/or megakaryoblasts. Thus, globoside appeared to be an interesting marker in CML-BC of the erythroblastic or mixed erythroblastic-megakaryoblastic type.
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PMID:A murine monoclonal IgM antibody specific for blood group P antigen (globoside) 242 10

Monocyte nonspecific esterase has been purified from cultured cells of the acute myeloid leukemia cell line, ML-1. The purified enzyme shows the characteristic properties of the monocyte neutral serine carboxyl esterase, with high sensitivity to organophosphorus inhibitors and sodium fluoride inhibitor. The enzyme is a membrane protein which in the native state exists as a monomer of a mol wt of approximately 68,000 and a trimer of mol wt 205,000. These forms exhibit a complex pattern of dissociation and reassociation based on apparent noncovalent binding of subunits. The delipidated dissociated enzyme runs as a single protein chain of a mol wt of approximately 62,000 on sodium dodecyl sulfate (SDS) gel electrophoresis. The relation of the subunits to monocyte isoenzymes seen on isoelectric focusing (IEF) and polyacrylamide gel electrophoresis at pH 9.5 (pH 9.5 PAGE) of cell extracts is demonstrated. Availability of purified enzyme allows development of monoclonal antibodies and analysis of myeloid differentiation. In addition, the substrate specificity and function of the purified monocyte ectoenzyme are being examined.
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PMID:Monocyte nonspecific esterase: purification and subunit structure. 301 85

The purpose of this study was to examine the expression and structure of CD22 in B cell precursor acute lymphoblastic leukemia (BCP-ALL), acute myeloid leukemia (AML), and T cell acute lymphoblastic leukemia (T-ALL). By using immunofluorescence microscopy and flow cytometry we observed that CD22 is expressed not only in the cytoplasm (as previously reported) but also on the cell surface of virtually all (15/16) BCP-ALL examined. CD22 that was biosynthetically labeled with 35S-cysteine and immunoprecipitated from the uncommon cytoplasmic CD22-positive/surface CD22-negative BCP-ALL cells was analyzed by single-dimension sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Our results indicated that the cytoplasmic form of CD22 comigrated with 125I/lactoperoxidase-labeled surface CD22. Therefore, cytoplasmic CD22 is probably a pool of fully processed glycoprotein. We also observed unusual cases of AML (approximately 20%) that expressed cytoplasmic CD22 based on immunofluorescent staining; however, biosynthetic labeling and immunoprecipitation revealed an apparently cross-reactive protein(s) of approximately 250 to 300 kd in AML cells. No T-ALL cell lines examined expressed either cytoplasmic or surface CD22. Thus, cytoplasmic and surface expression of bona fide CD22 appears restricted to B cells, which suggests that this molecule subserves a function unique to B cells.
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PMID:Expression and structure of CD22 in acute leukemia. 325 72

We studied the cellular uptake and retention of daunorubicin (D1) in two human leukemic cell lines (ML1 and K562) and myecloblasts from an untreated patient with acute myelogenous leukemia (AML). The rate of uptake and the steady-state level of D1 were not temperature dependent but increased markedly with increases in the pH of the medium. Also, saturation kinetics were not demonstrable using concentrations of D1 up to 111 microM. Together, these observation suggest a transport mechanism for D1 compatible with passive diffusion. Accumulation of D1 was increased only in cells from the AML patient with addition of sodium azide, whereas drug efflux was not increased significantly in the presence of glucose in MLI or K562 cells. Although the rate of uptake and steady-state levels of D1 were the same in these cells, metabolism and cytotoxicity of D1 differed. Our results indicate that ML1 cells can be used as a pharmacologic model for studying the metabolism and resistance of D1 in vivo.
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PMID:Comparative uptake, retention and cytotoxicity of daunorubicin by human myeloid cells. 345 68

The reactivity with monoclonal antibodies (MoAbs) specific for myelomonocytic cells and the expression of a particular esterase isoenzyme were analyzed in 159 cases of acute myeloid leukemias. The incidence of positivity of 16 MoAbs (MCS-2, MCS-1, OKM1, My-1, Leu-M1, Leu-M3, CA-2-38, MY4, MY7, MY8, MY9, VIM-D2, VIM-D5, Mo1, Mo2, 63D3) was studied using the indirect immunofluorescence technique. A carboxylic esterase isoenzyme which can be inhibited completely and selectively by sodium fluoride (NaF) was demonstrated by isoelectric focusing on horizontal polyacrylamide gels. This NaF-sensitive isoenzyme indicated the monocytic origin of the blast cells as it is specific for this cell lineage. Prior to the immunological-isoenzymatic analysis all cases were categorized into two subtypes according to morphological criteria of the FAB classification system: 147 cases of AML (FAB M1-3) and 12 cases of AMMoL/AMoL (FAB M4/5). However, 15 out of 147 cases of AML expressed the NaF-sensitive isoenzyme and were therefore assigned to the group AMMoL/AMoL. Likewise, 1 case, diagnosed morphologically as AMMoL, was negative for this marker isoenzyme and was assigned to the other leukemia subtype. The incidence of reactivity varied widely for the MoAbs tested regarding the overall results on all cases and the positivity of cases of either AML or AM-MoL/AMoL. The MoAbs were grouped into four classes depending on the pattern of reactivity with myeloblastic or monoblastic or both subtypes of acute myeloid leukemia. The MoAbs MCS-2, MY7, Leu-M1, and MY9 detected the vast majority of cases with either myelocytic or monocytic involvement (group-I: "pan-myelomonocytic" reactivity). The MoAbs MCS-1, OKM1, VIM-D5, and Mo1 showed a predominance in their staining pattern for monocytic variants, but were also positive on a substantial percentage of nonmonocytic cases (group-II: predominantly reactive with monocytic, but also myelocytic cases). The MoAbs Leu-M3, MY4, VIM-D2, Mo2, and MY8 reacted with the large majority of AMMoL/AMoL cases and with a small number of AML cases (group-III: monocyte-"specific" reactivity). The MoAbs of group-I are useful in differentiating acute lymphoid from acute myeloid leukemias. The MoAbs of group-III, and to a lower extent those of group-II, will be of considerable value in the subtyping of acute myeloid leukemias. The results show that accuracy of leukemia classification might not always be achieved by morphology alone, but that immunological and biochemical aspects should be included as well, and several MoAbs are very useful tools for classification and subtyping of acute myeloid leukemias.
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PMID:Reactivity patterns of monoclonal antibodies positive on myelomonocytic leukemia cells as defined by esterase isoenzyme analysis. 345 29

The antigen defined by MCS-2 monoclonal antibody (mAb) was characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of surface and internally labeled cells. Surface iodination revealed that MCS-2 antigen on the surfaces of acute myelogenous leukemia cells, HL-60 cells, and polymorphonuclear leukocytes (PMN) had the same molecular weight (Mr 150,000) and that their autoradiographic bands were also the same. Internal labeling of HL-60 cells with [35S]methionine followed by immunoprecipitation revealed two bands whose molecular weights were 150,000 and 130,000. HL-60 cells gave stronger bands than did PMN. The intensity of the Mr 130,000 band became weaker, when internally pulse-labeled cells were cultured in the absence of labeled methionine, suggesting that Mr 130,000 glycoprotein was a precursor protein of Mr 150,000 glycoprotein. MCS-2 mAb precipitated two bands from tunicamycin-treated HL-60 cells whose apparent molecular weights were 100,000 and 110,000. When cells were cultured with MCS-2 mAb, expression of the antigen decreased rapidly (within 10 min). The degree of suppression was more prominent in PMN than in acute myelogenous leukemia and in myelomonocytic cell lines. Reexpression of MCS-2 antigen by PMN after removal of the mAb from the culture medium was not observed, but it occurred rapidly in myelomonocytic cell lines, although it was blocked by pretreatment of the cells with cycloheximide. These findings suggested that the less-marked suppression of MCS-2 antigen expression by cell lines was due to its greater synthesis by these cells. These findings suggested that MCS-2 mAb reacted with identical molecules, which were recognized by other mAbs belonging to CD13. Furthermore, modulation of MCS-2 antigen was observed by MCS-2 mAb itself.
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PMID:Biochemical and functional characterization of MCS-2 antigen (CD13) on myeloid leukemic cells and polymorphonuclear leukocytes. 347 35

EO-1, an IgGl murine monoclonal antibody raised against human eosinophilic leukemia cells, reacts with eosinophils, basophils, platelets, and a few (2%) mononuclear cells but not with neutrophils. In the bone marrow, mature and immature eosinophils and basophils express the EO-1 antigen, whereas immature myeloid cells do not. The distribution of EO-1 antigen on leukemic cells is concordant with this finding, ie, typical myeloid lines (HL-60, KG-1, and ML-1) and fresh acute myelogenous leukemia cells are all unreactive with EO-1. Immunoprecipitation of an extract from surface-131I-labeled platelets with EO-1 and sodium dodecyl sulfate polyacrylamide gel electrophoresis, under reducing or nonreducing conditions, yielded a specific band of molecular weight 23,000. Previously described monoclonal antibodies reacting with eosinophils also recognize neutrophils. EO-1 is a unique antibody with specificity restricted to eosinophils, basophils, and platelets and might therefore be a valuable reagent for the study of their function and differentiation.
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PMID:A monoclonal antibody reactive with human eosinophils. 348 29


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