Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To ascertain whether progression from the chronic to the accelerated and blastic phases of chronic myeloid leukemia (CML) is associated with the loss of the myeloid differentiation antigens of the neutrophil granulocytes (NG), we analyzed two monoclonal antibodies (PMN 31D8 and PMN 13F6) recognizing normal peripheral blood NG membrane antigens in 49 patients in different evolutive stages of CML. Since five patients were studied twice, a total of 54 studies were carried out. Fourteen patients were evaluated at diagnosis, 12 in the controlled chronic phase within 1 year from diagnosis, 14 in the advanced chronic phase (median evolution 3.25 years), and 14 in the accelerated (five cases) or blastic (nine cases) phases. Fourteen normal subjects served as a control group. At diagnosis, a significant decrease in the positivity for both antigens was observed with respect to controls, probably due to the circulation of incompletely mature NG. In the early chronic phase the values were within the normal range, whereas a significant decrease was registered in the advanced chronic phase and especially in the accelerated/blastic phase. A negative correlation between the NG positivity for both markers and the time elapsed from the moment of obtaining the initial control of the disease was found, suggesting that a progressive loss of the myeloid antigens of the NG occurs during the evolutive course of CML. These results seem to confirm the usefulness of the NG myeloid differentiation antigen study as an evolutive parameter in CML.
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PMID:A study of the myeloid differentiation antigens of the peripheral blood neutrophil granulocytes in the different evolutive phases of chronic myeloid leukemia. 185 85

The immunophenotype (a), ultrastructural features (b) and cell kinetics (c) of circulating megakaryoblasts have been studied in two cases of pure megakaryoblastic and one case of mixed (myeloblastic, megakaryoblastic) cell proliferation in chronic myeloid leukaemia (CML). (a) The blast cells showed early megakaryocyte differentiation antigen (HLA-DR), platelet specific GpIIIa (CD61) and GpIIb-IIIa (CD41) antigens in different percentages. (b) The megakaryoblasts were recognized by the presence of platelet GpIIIa (CD61) demonstrated by an immunoelectron microscopic method. The labelled cells were "lymphocyte-like" megakaryoblasts and cells with features of cytoplasmic maturation (demarcation membranes, alpha granules and vacuoles). (c) Cellular DNA content of the megakaryoblasts was measured by propidium iodide (PI) staining of cells expressing platelet GpIIIa (CD61). Flow cytometric (FC) DNA analysis revealed no aneuploidy and high ploidy (greater than 4N) cell population. In the two cases of pure megakaryoblastic proliferation a high percentage of the megakaryoblasts were in the S-phase, while the non-megakaryoblastic cell fraction showed no elevated S-phase compartment. It is concluded that in CML the circulating megakaryoblasts (1) have a nuclear maturation arrest and accumulation at the level of tetraploid DNA content, (2) surface antigen expression and cytoplasmic organelles show a tendency to mature and (3) in pure megakaryoblastic proliferation the myeloid cells are not in the cell compartment showing high proliferation.
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PMID:Morphologic and flow cytometric analysis of circulating megakaryoblasts in chronic myeloid leukaemia. 192 49

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.
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PMID:Monoclonal antibody M195: a diagnostic marker for acute myelogenous leukemia. 272 60

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.
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PMID:Human monoclonal antibodies reactive with human myelomonocytic leukemia cells. 292 15

A monoclonal antibody (anti-BL4) recognizing a previously characterized Mr 54,000 glycoprotein (gp54) was developed by immunizing BALB/c mice with cells from a precursor B-cell line (Josh-7). In normal individuals, this antigenic molecule was present on tonsillar B-cells (60-80%) and on a fraction of peripheral blood B-cells (5-25%). BL4 (gp54) expression was investigated in 186 patients with a variety of hematological malignancies using indirect immunofluorescence and flow cytometric analysis. Twenty-six of 37 cases of B-cell chronic lymphocytic leukemia (CLL) and 18 of 33 cases of B-cell non-Hodgkin's lymphoma were BL4 positive. Surface expression of BL4 on reactive cases of CLL and non-Hodgkin's lymphoma was brighter than those of B1, B2, and B4, BL4 positive CLL cases expressed a higher proportion of mouse rosette forming cells and Leu-1 positive cells than the BL4 negative subgroup and were not associated with elevated serum immunoglobulin levels. Four of 7 BL4 negative CLL cases were associated with increased serum levels of immunoglobulin M. Lymphoblasts from 14 of 14 cases of non-T acute lymphoblastic leukemia and 3 of 3 pre-B lymphoid blast crisis of chronic myeloid leukemia were BL4 negative. Neoplastic cells from 2 of 3 cases of Waldenstrom's macroglobulinemia and 4 of 7 cases of hairy cell leukemia were BL4 reactive. None of 7 cases of multiple myeloma and plasma cell leukemia were BL4 positive. All 11 T acute lymphoblastic leukemia cases, 6 other T-cell malignancies, 5 cases of Hodgkin's disease, 51 cases of acute nonlymphocytic leukemia, and 9 cases of chronic myeloid leukemia in chronic phase thus far studied were BL4 negative. An in vitro induction experiment using phorbol ester on a case of B-CLL demonstrated disappearance of BL4 accompanied with further B-cell differentiation. Our study further substantiates the previous finding that gp54 is a differentiation antigen restricted to the B-cell lineage and expressed during the intermediate stage of B-cell ontogeny.
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PMID:Cellular distribution of a B-cell specific surface antigen (gp54) detected by a monoclonal antibody (anti-BL4). 309 65

We have previously reported the isolation of a monoclonal antibody (NHL-30.5) that reacts with an antigen expressed on a substantial proportion of marrow and blood cells of most patients with newly diagnosed or relapsing acute myeloid leukemia. This antigen is also found on several cell lines derived from myeloid malignancies of human origin. It is not present on mature hemopoietic cells or on the majority of differentiating bone marrow cells. In order to determine whether the NHL-30.5 antigen may, nevertheless, be expressed on low-frequency primitive normal hemopoietic cells, not detected in standard antibody screening procedures, its expression was studied on clonogenic erythropoietic and granulopoietic cells. Light-density (less than 1.077 g/mL) suspensions of normal or chronic myelogenous leukemia bone marrow and peripheral blood cells were stained with NHL-30.5 and fluorescein isothiocyanate labeled second antibody and then sorted into two fractions using the fluorescence-activated cell sorter. The first contained the top 5% of cells with the highest fluorescence intensity. The remainder were collected in the second fraction. Colony assays of both fractions showed the first to be enriched in CFU-E, BFU-E, and CFU-C content (fourfold to 17-fold). The second fraction was correspondingly depleted of these progenitors. These findings reveal NHL-30.5 antigen expression to be a transient event during normal hemopoiesis that characterizes primitive hemopoietic cells on several pathways. Subsequent experiments showed that the presence of up to 10 micrograms/mL of purified NHL-30.5 antibody in colony assay cultures neither inhibited nor stimulated colony formation. Marrow fibroblasts (subcultured marrow adherent cells) were NHL-30.5 negative. Immunoprecipitation studies showed that the antigen detected by NHL-30.5 is clearly distinct from that identified by My-10, another monoclonal antibody that has previously shown some similarities to NHL-30.5. It thus appears that the NHL-30.5 antibody reacts with a new myeloid differentiation antigen of as yet unidentified function that is normally restricted in its expression to early stages of hemopoiesis.
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PMID:Restricted expression of a new acute myelogenous leukemia-associated antigen (NHL-30.5) on normal hemopoietic progenitor cells. 345 4

BALB/c mice were immunized with uninduced K562 erythroleukemia cells and hybridomas were isolated after fusion of immune spleen cells to P3/NS1 murine myeloma cells. One selected hybrid, designated 10L-30, secreted an antibody of subclass immunoglobulin G2a which was specific for hematopoietic cells. Analysis of 10L-30 binding by complement-mediated cytotoxicity, indirect immunofluorescence, solid-phase radioimmunoassay, and mixed hemadsorption assay indicated that the 10L-30 antigen was expressed on the myeloid cell lines K562, KG-1A, KG-1, some B- and T-lymphoid cell lines, and all normal human peripheral blood T-lymphocyte samples tested, but was absent on the more differentiated myeloid cell lines HL-60, ML-2, ML-3, and normal blood granulocytes. Induction of erythroid differentiation in hemin-treated K562 cells caused a 10-fold reduction in 10L-30 binding. Human erythroid and granulocytic progenitor cells, platelets, erythrocytes, and reticulocytes were nonreactive, as were a variety of nonhematopoietic human tumor cell lines. Freshly isolated leukemic bone marrow samples from patients with M5 (2 of 5), M6 (2 of 2), acute lymphoid leukemia (9 of 14), and chronic myeloid leukemia in lymphoid blast crisis (1 of 1) were 10L-30 positive. The combined evidence indicates that the 10L-30 antigen is a normal, hematopoietic-specific differentiation antigen which is strongly expressed on both immature cells of the myeloid lineage and more generally in lymphoid ontogeny. The 10L-30 antigen may be a useful marker of both normal and leukemic hematopoietic differentiation.
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PMID:Distribution of a hematopoietic-specific differentiation antigen of K562 cells in the human myeloid and lymphoid cell lineages. 347 69

Three monoclonal antibodies raised against K 562, a cell line originally established from a patient with chronic myeloid leukemia (CML) in terminal blast crisis, were selected according to their distinct reaction pattern. Whereas two antibodies (ZIK-C1-A/C5 and ZIK-C1-A/H5 also designated C and H) recognized antigens, present on K 562 cells and other immature and mature hematopoietic cells (cell lines and normal blood and bone marrow cells), antibody ZIK-C1-A/D9 also designated Y showed an exclusive binding to K 562 cells. The results obtained (here and in the following paper) indicate, that antibody ZIK-C1-A/D9 defines an early differentiation antigen of hematopoiesis or a leukemia-associated antigen.
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PMID:Monoclonal antibodies against the human leukemia cell line K 562. 388 95

We describe an antigen(s) characterized by a heteroantiserum raised in rabbits against mature human granulocytes. This antigen was found on neutrophils, monocytes, platelets, acute and chronic myelocytic leukemia cells and on granulocyte-macrophage progenitor cells grown in agar. It was not found on lymphocytes, eosinophils, erythrocytes, or erythroid progenitor cells. On the basis of tissue distribution and absorption studies, the antigen (tentatively designated the "myelo-monocytic" antigen) is distinct from antigens previously identified on human neutrophils. Restriction of the "myelo-monocytic" antigen to normal and malignant cells of the myelo-monocytic series suggests that it may represent a normal differentiation antigen of the myelo-monocytic lineage.
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PMID:An antigen expressed by cells of the myelo-monocytic lineage. 616 91

Two different Fc receptors for IgG (Fc gamma R) have been identified on human leukocytes: a high avidity receptor (Fc gamma Rhi) present on monocytes but not on neutrophils, and a low avidity receptor (Fc gamma Rlo) present on neutrophils but not on monocytes. Fc gamma Rlo can be inhibited and the receptor precipitated by monoclonal antibody 3G8. We have used this monoclonal antibody to study the course of Fc gamma Rlo appearance on bone marrow cells, leukocytes of patients with chronic myelogenous leukemia (CML), and HL-60 and U937 cells induced to differentiate with agents such as dimethyl sulfoxide (DMSO), retinoic acid, phorbol myristate acetate, and lymphokine. We report that Fc gamma Rlo is a late differentiation antigen, first expressed at the metamyelocyte stage. Since precursors to metamyelocytes bear Fc gamma R, and the promyelocyte line HL-60 bears Fc gamma Rhi, there must be a progressive loss of Fc gamma Rhi during myeloid differentiation and the reciprocal expression of Fc gamma Rlo. Results of immunoprecipitation and polyacrylamide gel analysis of the proteins are consistent with these results. We have also studied the receptor for the C3bi complement component (CR3), which is blocked and immunoprecipitated by monoclonal antibody OKM10. During DMSO-driven differentiation of HL-60 cells, we find that CR3 is induced on all cells, whereas Fc gamma Rlo is induced on only 24% of cells, suggesting that CR3 appears earlier during differentiation than Fc gamma Rlo does.
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PMID:Ontogeny of Fc receptors and complement receptor (CR3) during human myeloid differentiation. 623 Mar 73


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