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)

The in vitro differentiation of cultured primary bone marrow cells from patients with acute promyelocytic leukemia (M3) and chronic myelocytic leukemia (CML) induced by retinoic acid (RA) and TPA was studied. The results indicated that both the M3 and CML bone marrow cells bipotently differentiated into either myeloid or macrophage-monocytic lineage in response to the inducers. On M3 cells the effect of TPA was more potent than RA, and TPA could inhibit the phenotype of myeloid terminal differentiation induced by RA but not vice versa. However, RA could overcome the TPA-induced inhibition of myeloid terminal differentiation of CML cells. These experiments provide a useful model for studying the molecular mechanism of hematopoietic cell differentiation.
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PMID:[Retinoic acid and 12-0-tetradecanoylphorbol-13-acetate (TPA) inducing bipotent differentiation of cultured primary bone marrow cells from leukemia patients]. 188 36

Poly(A) polymerase activity was markedly elevated in CML in the blastic phase, moderately high in the accelerated phase and low in the chronic phase. The activity was significantly higher in the myeloid crisis than in the lymphoid crisis and elevated with increasing ratio of blasts in leukemia cases. In TPA or retinoic acid-treated leukemia cells poly(A) polymerase activity was decreased. These results suggest that poly(A) polymerase activity changes, depending on the maturation of leukemic cells and the assay of this enzyme activity may be useful for the early detection of the exacerbation of CML cases.
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PMID:Polyadenylic acid polymerase activity in chronic myelogenous leukemia. 215 15

Two spontaneous outgrowing Epstein-Barr virus (EBV)-carrying lymphoblastoid cell lines (LCLs), CG2 and CG3, have been established from bone marrow cells of myeloid leukemia patients. CG2 was derived from a patient with chronic myelomonocytic leukemia (CMMoL) and who has a 45 XO karyotype. CG3 was derived from a patient with juvenile chronic myeloid leukemia (CML) and who carries a hypotetraploid karyotype, 91XXYY. Both CG2 and CG3 cells carry the same type of translocation; t(1;19)(q23;p13). Both cell lines are of an early B cell lineage as shown by their reactivities with monoclonal antibodies OKIa, B1, B2 and B4. The combination of horizontal discontinuous agarose slab gel and Southern hybridization results show CG2 and CG3 cells are of monoclonal origin and harbor episomal EBV genomes. Approximately 50 EBV genome equivalents were contained in CG2 and CG3 cells. Immunofluorescence studies demonstrate the expression of EBV-encoded antigen (EBNA) in almost all cells of these two lines. The expression of EA and VCA is only observed in a small percentage of cells and cannot be induced by treatment with TPA and SB. Therefore, CG2 and CG3 cells are probably nonproducer cell lines for EBV. The serum samples from both patients have been shown to contain elevated IgG antibody titers to EBV antigens. Both cells are found to be nontumorigenic in nude mice. These cells may provide an important tool in analyzing molecular epidemiological aspects of EBV infections in diseases such as CMMoL and juvenile CML.
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PMID:Characterization of two newly established EBV-containing lymphoblastoid cell lines from patients with myeloid leukemias. 215 89

The effects of TPA (12-0-tetradecanoylphorbol-13-acetate) and RA (retinoic acid) were investigated on the cell lines HL60 (acute promyelocytic leukemia) and K562 (erythroleukemia) and on cells from patients with several kinds of leukemia. There were 14 cases of acute lymphocytic leukemia (ALL), 2 cases of chronic lymphocytic leukemia (CLL), 23 cases of acute myeloid leukemia (M1-M7), 5 cases of chronic myelocytic leukemia in blast crisis (CML-BC) and 2 mixed leukemias. In almost all of the cases examined, after TPA exposure cells from patients with proven myeloid leukemia became adherent to the substrate, while lymphoid leukemia cells remained in suspension, allowing the differentiation of lymphoid from myeloid blasts. The only exception was in one case of CLL, which had cells that became adherent with long filamental projections. In addition, increased phagocytosis following TPA exposure permitted characterization of M7 as this was the only myeloid leukemia negative for phagocytosis. Further discrimination between the subtypes of myeloid leukemia could be based on the increased lysozyme production seen after TPA in M4 and M5. Esterase positivity allowed the discrimination of M1 cells, which were negative before and after TPA treatment. In agreement with the results of other authors, TPA and RA led to independent ways of differentiation, granulocytic-like lineage and monocytic-like cells being favored by RA and TPA, respectively. The capacity of the same cell to differentiate into more than one lineage, depending on whether RA or TPA was used, was only seen in the present study with M3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myeloid leukemia differentiation by phorbol ester and retinoic acid: a practical approach. 223 Nov 80

Cytofluorographic analysis of surface immunoglobulin (sIg) light chain clonal excess (CE), defined as (%kappa+ - %lambda+)/(%kappa+ + %lambda+) cells per discrete level of fluorescence intensity, was carried out on mononuclear cells of 32 leukemic patients. Eight demonstrated sIg light chain CE, including four blastic chronic myeloid leukemias (BL-CML), three "null" acute lymphoblastic leukemias (ALL), and one leukemic lymphoblastic lymphoma. Six of the leukemias demonstrated a kappa CE and two had a lambda CE. Sorted kappa+ PB cells from a BL-CML patient were shown to have a diploid DNA stem line and to bear the "common" ALL antigen. To provide further support for our finding of the expression of sIg light chains in ALL, we studied the REH cell line, derived from a "common" ALL patient and found cytoplasmic mu heavy chain and surface Ig lambda CE. Nucleic acid blotting experiments on REH revealed that both kappa genes had been deleted and that lambda genes had been rearranged, as expected in B cells expressing lambda light chains. Moreover, REH cells contained mu and lambda RNA. When REH cells were treated with TPA the amount of mu chain RNA increased by approximately fivefold and the amount of lambda chain RNA increased by approximately twofold. The finding of sIg light chain in pre-B cell leukemias and in the REH cell line, suggests that these leukemic cells are further differentiated along the B-cell lineage than was previously believed.
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PMID:Surface immunoglobulin light chain expression in pre-B cell leukemias. 242 86

Most Hodgkin's mononuclear cells and Reed-Sternberg (H-RS) cells are characterized by the expression of the antigen CD30, but not of T or B cell markers. A few H-RS cells, however, may express a limited number of T or B cell markers. Whether this expression is sufficient to allow the conclusion that H-RS cells are derived from T and/or B cells has been debated vigorously. The present study examined whether CD30 and aberrant T and B cell markers are expressed in cell lines that are well documented as being derived from the granulocyte/monocyte/histiocyte lineage. These cells included HL-60, KG-1, ML-1, THP-1, and U-937. Four other cell lines derived from patients with leukemias/lymphomas of monocytic or granulocytic origins also were studied. These cells included BV173, CML-Brown, CTV-2, and SU-DHL-1. If aberrant expression is detected, by analogy one may expect that rare T or B cell marker expression may occur in H-RS cells, because abundant evidence has indicated that H-RS cells may be related to cells in histiocyte lineage. In all nine of the cell lines studied, it was confirmed that numerous monocyte/granulocyte markers were expressed. The marker expression was enhanced after cells were induced to differentiate with phorbol ester (TPA) and tumor necrosis factor (TNF). It was noted that several T and B cell markers also were expressed by these cells. Unlike the expression of monocyte/granulocyte markers, the expression of T or B cell markers was not affected, or only minimally affected, by treatment of the cells with TPA or TNF. Five of the cell lines (BV173, CML-Brown, CTV-2, SU-DHL-1, and THP-1) were shown to be CD30-positive. In CTV-2 and BV173, the expression of CD30 was greatly increased after induction with phorbol ester or TNF. Based on these studies, the following conclusions were reached: 1) The expression of aberrant B or T cell markers is not an uncommon finding in granulocyte/monocyte/histiocyte-related neoplastic cells. 2) The expression of granulocyte/monocyte markers in these cells is related to the state of cell differentiation, whereas the expression of T or B cell markers is not. 3) CD30 is not necessarily a proliferation-related antigen, and its expression is not a sole property of T or B cells, but can be present in granulocyte/monocyte/histiocyte-related cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Aberrant expression of T cell and B cell markers in myelocyte/monocyte/histiocyte-derived lymphoma and leukemia cells. Is the infrequent expression of T/B cell markers sufficient to establish a lymphoid origin for Hodgkin's Reed-Sternberg cells? 249 2

The in vitro induced differentiation of a number of human leukemia cell lines by chemical inducers not only provides a valuable model system for the study on the mechanism of hematopoietic cell proliferation and differentiation at both cellular and molecular levels, but also reveals a new prospect in the treatment of leukemia. In order to find out the possibility of applying inducing agents to the patients with various types of leukemia, the bone marrow cells in primary culture from 50 patients with leukemia were tested for their inducibility in response to the inducers. Only M3 leukemia bone marrow cells can be markedly induced by retinoic acid to the myeloid terminal cells with positive NBT reduction while the cells of other types respond with uncertainty. TPA is able to cause a macrophage-like differentiation in bone marrow cells of all types of leukemia except M1. However, the leukemic cells of chronic myelogenous leukemia in lymphocytic blast crisis will lose response to TPA. The cultured bone marrow cells of acute lymphocytic leukemia respond neither to retinoic acid nor to TPA. Homoharringtonine, a chemotherapeutic drug used in the so-called HOAP regimen for acute nonlymphocytic leukemia, seems to possess the capability of inducing HL-60, the promyelocytic leukemia cell line, to NBT positive myeloid terminal cells, although the inducing effect is weaker than retinoic acid.
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PMID:Heterogenous response of primary cultured bone marrow cells of patients with different varieties of leukemia to differentiation inducers. 250 3

The expression of the myeloperoxidase (MPO) gene was studied, by means of Northern blot analysis in 14 cases of acute myeloid leukemia (AML), 11 cases of chronic myeloid leukemia (CML), and 6 cases of CML blast crisis, and in HL60 cells before and after induction of terminal differentiation with retinoic acid (RA), phorbol esters (TPA), or vitamin D. The expression of a panel of cell cycle-related genes, namely C-MYC, histone H3, ornithine decarboxylase, P53, vimentin, and calcyclin, was also studied in the same cell populations. Our results indicate that: (a) MPO gene expression (steady state mRNA levels) is strictly confined to the first stages of myeloid differentiation, reaching its peak at the promyelocyte stage and becoming undetectable in mature granulocytes and monocytes; (b) cells devoid of any detectable MPO enzymatic activity such as leukemic basophils have a high content of MPO mRNA; and (c) MPO gene expression is not related to the growth activity of the cell population. Finally, our results show that the pattern of expression of growth-regulated genes in the neoplastic myeloid disorders AML, CML, and CML blast crisis is remarkably different.
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PMID:Expression of the myeloperoxidase gene in acute and chronic myeloid leukemias: relationship to the expression of cell cycle-related genes. 254

It is a widely held theory that the bcr-abl hybrid gene plays an active role in chronic myelogenous leukemia (CML). The bcr-abl gene product (P210bcr-abl) is a structurally altered and enzymatically activated form of the normal c-abl gene product. P210bcr-abl is expressed in two cell lines derived from CML patients in blast crisis: K562 and EM2. Activation of protein kinase C by the strong tumor promoter TPA induced dramatic changes in K562 cells. We have shown that exposure of K562 cells to low concentrations (10 nM) of TPA stopped cell division and sharply reduced the expression of P210bcr-abl. In contrast, similar treatment of EM2 cells resulted in a slightly increased proliferation rate and stimulation of P210bcr-abl expression. A second tumor promoter, mezerein, also dramatically reduced P210 levels in K562 cells and elevated them in EM2 cells. These observations establish that expression of the bcr-abl gene can be either increased or decreased, depending on the cell type, and that these effects correlate with the proliferative state of the cell. These results are consistent with the hypothesis that P210bcr-abl plays an important role in the maintenance of CML.
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PMID:Differential effects of tumor promoters on P210bcr-abl expression. 268 23

The effect of LD Ara-C (10(-8) mol/l) (Ara-C), TPA (1.6 x 10(-7) mol/l) and 13-cis-retinoic acid (RA) (10(-6) mol/l) on the differentiation in liquid culture of bone marrow cells from 5 patients with acute lymphoblastic, 17 patients with acute myelogenous leukemia, 1 patient in myeloid and 1 in lymphoid crisis of chronic granulocytic leukemia was studied. Ara-C induced morphological and cytochemical differentiation into monocytic cells in 2 cases (M1, M5 type). TPA induced convincing morphological and cytochemical features of maturation into monocytic cells in 4 cases (two M1, one M2, and one M5 type) and into differentiated myeloid cells in 2 cases (M1, M4 type). RA in one case (M2 type) out of three AML studied induced cytochemical and immunocytochemical features of maturation. The results of the study indicate that although TPA is a better inducer of blast cell differentiation than Ara-C, however, neither is a potent differentiation agent of leukemic blasts in liquid culture. The heterogeneity of leukemic blasts within the same type of leukemia was confirmed by their different response to differentiating agents.
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PMID:Study of differentiation of fresh human leukemic cells by low dose cytosine arabinoside (LD Ara-C) and 12-O-tetradecanoylphorbol-13-acetate (TPA). 281 52


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