UMLS:C0023467 - FACTA Search

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)

Thirty-six cases of acute myeloid leukaemia (AML) were tested with a large battery of monoclonal antibodies (moAbs) detecting surface markers normally expressed by myelomonocytic, T and B lymphoid, megakaryocytic and erythroid lineages. Differences in antigenic expression were observed among the various FAB subgroups: HLA-class II molecules were found in almost all AML cases but not in the promyelocytic subgroup (M3); CD14 and CD36 antigens were detected in monocytic leukaemias (M4 and M5); the CD34 moAb (MY10) recognizing an epitope described on myeloid stem cells was positive in 88% of the M1 and 80% of the M3 cases. By a multivariate analysis, only the CD14b (MY4) discriminated significantly between M1-M2 and M4-M5 subgroups. Using Cox's model to assess the prognostic importance of variables including immunophenotyping on survival, we undertook a one by one analysis and found that the presence of CD17 antigen predicted for a shorter survival (P = 0.03). In addition this marker appeared more significant than other clinical and biological parameters.
...
PMID:Diagnostic and prognostic significance of myelomonocytic cell surface antigens in acute myeloid leukaemia. 260 21

A murine monoclonal antibody LK-1 reacting with the common leukocytic antigen gp 95 was prepared by means of standard hybrid technology. This antigen was found in wider distribution on various morphologic types of human blood cells of the monocytic, granulocytic, thrombocytic, erythroid and lymphoid series (with the exception of some B lymphocytes). Furthermore, the monoclonal antibody reacted with the antigen occurring on leukaemic cells of patients with AML, CML, AMMoL, ALL and AMoL and reacted with cells of some human cell lines as well.
...
PMID:[Reactivity of LK-1 monoclonal antibodies with human hematopoietic cells]. 261 25

Four monoclonal antibodies against human erythrocyte membrane antigens were established. The antigenic determinants of KOR-E1, E3, E6 were Pr1h antigen, Wrb antigen, and the trypsin sensitive portion of glycophorin A (EnaTS) respectively. The antigen recognized by KOR-E4 could not be determined. The reactivities of these antibodies with normal hematopoietic cells, malignant hematopoietic cell lines (N = 31), and fresh leukemic cells obtained from 128 patients with various types of leukemias were studied. All antibodies reacted only with erythrocytes among peripheral blood cells, and also KOR-E6 reacted only with erythroid cells among bone marrow cells. KOR-E3 had no reactivity with any cell lines examined, and KOR-E1 and KOR-E4 were reactive with some lymphoid cell lines. However, KOR-E6 had specific reactivities with erythroid (HEL, K562), megakaryocytic (CMK-1), multiphenotypic (KOPM-28), and basophilic (KU-812) cell lines. The antigen (glycophorin A) recognized by KOR-E6 was expressed on a small population of mononuclear cells separated from acute lymphoblastic leukemia (3/70), acute myelogenous leukemia (2/12), monosomy 7-myeloproliferative disorder (1/1), juvenile CML (1/1), and transient myeloproliferative disorder with Down's syndrome (4/12), although it could not be determined whether these cells were leukemic cells or not. KOR-E6 was reactive with a large population of leukemic blasts in erythroleukemia (2/2) and acute megakaryoblastic leukemia (3/6). Thus, KOR-E6 appears to be an erythroid marker of leukemic cells.
...
PMID:[Monoclonal antibodies against human erythrocyte membrane antigens and their reactivities with hematopoietic cells]. 261 36

The abilities of human recombinant IL-3, GM-CSF, G-CSF, M-CSF and Epo to induce maturation in human AML cells in vitro were investigated using cell specimens from 25 AML patients. The experiments were carried out under exactly defined serum-free culture conditions. In the absence of CSFs, monocytic and/or granulocytic maturation was detected in 14/25 cases. IL-3, GM-CSF, G-CSF and M-CSF elevated the proportions of monocyte/macrophages in 3/25, 2/25, 1/25 and 6/25 cases respectively, and increased the percentages of mature granulocytes in 2/25, 1/25, 1/25 and 0/25 cases, and if so only to a limited extent (values below 50%). The 3H-thymidine (3H-TdR) uptake studies revealed that IL-3, GM-CSF, G-CSF and M-CSF were efficient stimulators of DNA synthesis of AML cells in 19, 15, 13 and four of those cases, respectively. Thus, although the cells in most cases responded to CSFs by activation of DNA synthesis, they were unable to give rise to terminally differentiated stages. Provision of CSFs in combination was more frequently effective in enhancing maturation and also increased the magnitude of maturation response. Monocytic versus granulocytic maturation of AML cells after culture did not correlate with the FAB cytology nor with the type of CSF presented; but generally granulocytic maturation was an infrequent phenomenon. Epo stimulated erythroid differentiation and DNA synthesis only in the case of erythroleukaemia, but it had no effect on the cells of 10 other AML cases. Extrapolation of these in vitro findings would suggest that CSFs would have a limited therapeutic utility to induce AML cell maturation in vivo and that hazards of stimulating blast cell proliferation with these factors may be anticipated.
...
PMID:Maturation of human acute myeloid leukaemia in vitro: the response to five recombinant haematopoietic factors in a serum-free system. 264 40

Recently we reported that two monoclonal antibodies (MoAbs), H25 and H366, which react with human natural killer cells and monocytes, also react with normal in vitro colony-forming cells including granulocyte-monocyte colony-forming units (CFU-GM), erythroid burst-forming units (BFU-E), and erythroid colony-forming units and with leukemic blasts in preliminary testing of cells from patients with myeloid leukemias and T cell acute lymphocytic leukemia. In the present studies we examined the reactivities of MoAbs H25, H366, and MY9 (singly or combined) with the total leukemic cell population and the leukemic clonogenic cells (L-CFC) from 28 patients with acute myeloblastic leukemia. Using cytofluorography, we found the extent of expression of antigen H25 comparable to MY9 in the majority of patients, and both were more highly expressed than antigen H366. Incubation with H25 and H366 MoAbs simultaneously did not increase the number of positive cells over that seen when stained with H25 alone; however, the amount of antibody fluorescence intensity (FI) was increased. Leukemic cells simultaneously stained with MoAbs H25, H366, and MY9 displayed the highest number of positive cells and FI. Using magnetic beads coated with sheep anti-mouse IgG for depleting antibody-binding cells, greater than or equal to 90% of L-CFC were depleted by a combination of H25 and H366 MoAbs in 76% of AML cases tested as compared to 41% of the cases with MoAb MY9. Using a MoAb cocktail of H25, H366, and MY9, greater than or equal to 90% of L-CFC were depleted in 94% of cases tested, and greater than or equal to 99% of L-CFC were removed in 76% of the cases. Using the same depletion methods for normal bone marrow cells, a combination of anti-H25 and anti-H366 removed 90%, 98%, and 84% of CFU-GM, BFU-E, and multipotent colony-forming units (CFU-GEM), respectively, whereas the cocktail of H25, H366, and MY9 MoAbs removed 98%, 99.5%, and 97% of CFU-GM, BFU-E, and CFU-GEM, respectively. Incubation of H25 and H366-depleted bone marrow cells for 2 weeks in the presence of irradiated adherent cell layers from long-term marrow cultures generated CFU-GM and some BFU-E, as did H25, H366, and MY9-depleted marrow cells, although to a much lesser extent. Based on the overall data, combinations of H25, H366, and MY9 MoAbs and immunomagnetic beads conceivably might have therapeutic potential for ex vivo elimination of leukemic cells from AML remission marrows prior to autologous transplantation.
...
PMID:Analysis of the individual and combined reactivities of monoclonal antibodies H25, H366, and MY9 with normal progenitor cells and blast cells from patients with acute myeloblastic leukemia. 265 31

Monoclonal antibody (mAb) M195 is a mouse IgG2a reactive with a myelomonocytic differentiation antigen found on early myeloid cells and monocytes. The reactivity of M195 with fresh hematopoietic neoplasms in the blood or bone marrow from 227 patients at Memorial Hospital was determined by flow cytometry. M195 was positive on 67% of 61 myeloblastic leukemias. Seventy percent of Tdt-negative ANLL and 30% of Tdt-positive ANLL were positive; 100% of CMMOL and 100% of CML in myeloblastic crisis or accelerated phase were positive. In contrast, M195 was positive on only 8% of 51 lymphoblastic leukemias and 1% of 70 other nonmyeloid samples. M195 binding did not correlate well with FAB classification of ANLL. The pattern of reactivity of M195 was similar but not identical to that of MY9 (CD33) on the same cases (83% concordance). Cross-blocking of M195 binding by MY9 and L4F3 (CD33) was demonstrated. M195 may bind to a different epitope on the same protein antigen. The presence of both MY9 and M195 positivity on a leukemia sample had a 98% specificity of diagnosing ANLL, which was greater than MY9 alone (88%) or M195 alone (92%). Assays of granulocytic-monocytic and erythroid colony-forming units showed M195 to be present on these hematopoietic progenitors. This pattern of reactivity of M195, together with its lack of reactivity with mature granulocytic elements or with adult tissues, make it a candidate for therapy of ANLL in vivo.
...
PMID:Monoclonal antibody M195: a diagnostic marker for acute myelogenous leukemia. 272 60

The outcome of treatment with standard first line therapy of 66 patients with acute myeloid leukaemia (AML) secondary to preceding chemotherapy (Group 1), a myelodysplastic state (Group 2) or a myeloproliferative disorder (Group 3) was analysed in relation to the preceding disorder, the cytogenetic pattern where available, and the cytology and cytochemistry of blood and bone marrow. The complete remission (CR) rate for the secondary AMLs was 36% (24/66), with 24% (16/66) dying in the induction period and 39% (26/66) having resistant disease. The CR rate was 25% (5/20) for Group 1, 42% (15/36) for Group 2, and 40% (4/10) for Group 3. Even after allowance for the generally older age of the secondary AML patients, they still had a significantly poorer CR rate than the de novo AMLs (P = 0.0004). The lower CR rate was chiefly due to resistant disease. Despite this, overall survival was not significantly worse for the secondary AML patients (P = 0.15). For the 36% that achieved remission, remission duration appeared similar to that of de novo cases. Of 62 cases with adequate cytology, 38 (61%) had evidence of erythroid and/or megakaryocytic dysplasia with a CR rate of 32% (12/38). The CR rate of these multineage leukaemias was not significantly different from that of the 24 (39%) who showed granulocyte/monocyte precursor involvement only, 42% (10) of whom achieved CR. The presence of features of differentiation within blast cells such as Auer rods or sudanophilia (greater than 50% positive blasts) was associated with a higher remission rate 47% (18/38) than that of poorly differentiated cases 17% (3/18) (P = 0.04) and thus appeared to be a more important determinant of CR achievement than was lineage involvement. Cases with a normal karyotype had a 33% (7/21) CR rate, while those with chromosomal abnormalities had a 37% (9/24) CR rate. Only 12 of the 45 cases with adequate cytogenetic analysis showed deletions or monosomies involving chromosomes 5 or 7, and seven of these were in Group 1.
...
PMID:AML associated with previous cytotoxic therapy, MDS or myeloproliferative disorders: results from the MRC's 9th AML trial. 273 42

Human granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine derived from activated T cells, endothelial cells, fibroblasts, and macrophages. It stimulates myeloid and erythroid progenitors to form colonies in semisolid medium in vitro, as well as enhancing multiple differentiated functions of mature neutrophils, macrophages, and eosinophils. We have examined the binding of human GM-CSF to a variety of responsive human cells and cell lines. The most mature myelomonocytic cells, specifically human neutrophils, macrophages, and eosinophils, express the highest numbers of a single class of high affinity receptors (Kd approximately 37 pM, 293-1000 sites/cell). HL-60 and KG-1 cells exhibit an increase in specific binding at high concentrations of GM-CSF; computer analysis of the data is nonetheless consistent with a single class of high affinity binding sites with a Kd approximately 43 pM and 20-450 sites/cell. Dimethyl sulfoxide induces a 3-10-fold increase in high affinity receptors expressed in HL-60 cells, coincident with terminal neutrophilic differentiation. Finally, binding of 125I-GM-CSF to fresh peripheral blood cells from six patients with chronic myelogenous leukemia was analyzed. In three of six cases, binding was similar to the nonsaturable binding observed with HL-60 and KG-1 cells. GM-CSF binding was low, or in some cases, undetectable on myeloblasts obtained from eight patients with acute myelogenous leukemia. The observed affinities of the receptor for GM-CSF are consistent with all known biological activities. Affinity labeling of both normal neutrophils and dimethyl sulfoxide-induced HL-60 cells with unglycosylated 125I-GM-CSF yielded a band of 98 kDa, implying a molecular weight of approximately 84,000 for the human GM-CSF receptor.
...
PMID:Characterization of the human granulocyte-macrophage colony-stimulating factor receptor. 282 52

Granulocyte/macrophage progenitor cells (CFU-GM) and erythroid progenitor cells (BFU-E) have been assayed in peripheral blood (PB) and/or bone marrow (BM) from 12 patients with acute lymphocytic leukemia (ALL), 16 patients with chronic lymphocytic leukemia (CLL) and 31 patients with various forms of non-Hodgkin lymphoma (NHL) without BM involvement. Progenitor cell growth in PB and BM from the NHL patients did not differ statistically from controls (p greater than 0.1). CFU-GM and BFU-E per ml PB were markedly increased in ALL and CLL patients (p less than 0.001) while CFU-GM and BFU-E per plated BM cells from these patients were severely depressed (p less than 0.001). Lymphoblasts from one ALL patient failed to inhibit CFU-GM and BFU-E-derived colony growth from control PB mononuclear cells. The high levels of circulating progenitor cells in ALL and CLL patients clearly distinguish them from other cytopenic hematological malignancies, in which decreased progenitor cell levels have been demonstrated previously (acute myeloid leukemia, hairy cell leukemia). The cause of this finding and its pathophysiological implication still remains to be established.
...
PMID:In vitro culture studies of granulocyte/macrophage and erythroid progenitor cells in lymphoproliferative disorders. 288 76

Peripheral blood mononuclear cells from a patient with chronic myelogenous leukemia (CML), in remission, were depleted of CD8-positive T-cells and cultured with Epstein-Barr virus. Four of 20 cultures (20%) secreted human IgG antibodies selectively reactive with the cell surfaces of certain human leukemia cell lines. Three polyclonal, Epstein-Barr virus-transformed, B-cell lines were expanded and fused with the human-mouse myeloma analogue HMMA2.11TG/O. Antibody from secreting clones HL 1.2 (IgG1), HL 2.1 (IgG3), and HL 3.1 (IgG1) have been characterized. All three react with HL-60 (promyelocytic), RWLeu4 (CML promyelocytic), and U937 (monocytic), but not with KG-1 (myeloblastic) or K562 (CML erythroid). There is no reactivity with T-cell lines, Burkitt's cell lines, pre-B-leukemia cell lines, or an undifferentiated CML cell line, BV173. Leukemic cells from two of seven patients with acute myelogenous leukemia and one of five with acute lymphocytic leukemia react with all three antibodies. Normal lymphocytes, monocytes, polymorphonuclear cells, red blood cells, bone marrow cells, and platelets do not react. Samples from patients with other diverse hematopoietic malignancies showed no reactivity. Immunoprecipitations suggest that the reactive antigen(s) is a lactoperoxidase iodinatable series of cell surface proteins with molecular weights of 42,000-54,000 and a noniodinatable protein with a molecular weight of 82,000. Based on these data these human monoclonal antibodies appear to react with myelomonocytic leukemic cells and may detect a leukemia-specific antigen or a highly restricted differentiation antigen.
...
PMID:Human monoclonal antibodies reactive with human myelomonocytic leukemia cells. 292 15

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>