Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have assessed whether tyrosine protein kinase (TPK) is involved in B cell differentiation. In vitro phosphorylation of an endogenous substrate in B cell leukemias showed that leukemic B cells at different stages of differentiation had specific endogenous substrates in tyrosine phosphorylation as well as distinct TPK activity. To clarify the relationship between TPK and the process of B cell differentiation, we studied protein tyrosine phosphorylation in two kinds of leukemic B cells, which showed distinct responses to TPA (12-O-tetradecanoylphorbol-13-acetate) in B cell differentiation. TPA-treated leukemic B cells from patients with B cell chronic lymphocytic leukemia (B-CLL) differentiated into cytoplasmic immunoglobulin (clg)+ plasmacytoid cells, while TPA-treated leukemic B cells from patients with hairy cell leukemia (HCL) did not differentiate into clg+ cells, but showed a peculiar morphological change, spreading. Untreated B-CLL cells and HCL cells showed similar TPK activities and tyrosine protein phosphorylation. When treated with TPA, enhanced phosphorylation was seen in B-CLL cells, while a clear reduction in phosphorylation was found in HCL cells. However, using 4-hydroxycinnamide derivatives which reduce TPK activity, we found that only the reduction of TPK activity did not lead HCL cells to spreading. These data suggest that protein tyrosine phosphorylation and/or dephosphorylation might be involved in B cell differentiation, but only the change of TPK activity in HCL cells is not sufficient to induce effects.
Leukemia 1990 Oct
PMID:Association of protein tyrosine phosphorylation with B cell differentiation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). 221 73

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)
 ...
PMID:Myeloid leukemia differentiation by phorbol ester and retinoic acid: a practical approach. 223 Nov 80

The neoplastic cells from 14 cases of hairy-cell leukemia were investigated in order to determine their membrane phenotype on the basis of their reactivity with a large panel of B-, T-, myeloid/monocytic- and non-lineage restricted monoclonal antibodies. The data were compared to those from monoclonal antibody studies on phorbol-ester (TPA) induced cells from 10 patients with B-type chronic lymphocytic leukemia. The study has so far revealed further evidence for the B-cell nature of hairy-cells leukemia and demonstrates a developmental link between the two cell types, suggesting that hairy-cells represent a more advanced differentiation stage along the B-cell lineage.
 ...
PMID:A comparison of membrane marker phenotypes in hairy-cell leukemia and phorbol-ester induced B-cll cells using monoclonal antibodies. 240 7

Serum-free culture conditions would be preferable when studying the cellular and molecular regulation of B lymphocyte activation, proliferation and differentiation. We describe here the morphological and functional differentiation of chronic B-lymphocytic leukaemia (B-CLL) cells from 10 patients cultured in serum-free medium. When exposed to the phorbol ester TPA, cells from 8/10 cases expressed blastoid morphology and secreted significant levels of monoclonal IgM. The addition of 0.5% newborn calf serum to the serum-free medium increased both the spontaneous and TPA-induced IgM secretion of B-CLL cells by a factor of 6 and 7, respectively. Compared with TPA, significant but lower levels of IgM secretion and morphological differentiation were observed with native purified leucocyte interferon-alpha (IFN-alpha) (6/8 patients), some batches of recombinant IFN-alpha 2 (5/8 patients) and recombinant IFN-gamma (4/8 patients) in a dose-dependent and specific manner. Preactivation of B-CLL cells with TPA or anti-mu antibody was not necessary for the IFN-induced functional maturation. Significant DNA synthesis was not observed with any of the inducers used. These studies show that B-CLL cells can be induced to differentiate under serum-free conditions in response to physiological and non-physiological ligands.
 ...
PMID:Induction of IgM secretion by chronic B-lymphocytic leukaemia cells in serum-free medium: effects of interferon-alpha, -gamma and phorbol ester. 245 Jul 4

A 72-year-old man with refractory anemia (RA) developed overt megakaryoblastic leukemia after the course of RA with excess of blasts. The blasts were positive for platelet peroxidase activity and had platelet glycoproteins (GPs) such as GPIIb/IIIa and GPIIIa. The bone marrow biopsy at terminal stage disclosed marked fibrosis. The nature of the megakaryoblasts was investigated. The blasts did not differentiate morphologically into mature megakaryocytes with TPA addition. In vitro colony assay showed the failure of colony-forming unit, megakaryocyte growth in peripheral blood. The pathogenesis of myelofibrosis in our patient is discussed.
 ...
PMID:Refractory anemia terminating in acute megakaryoblastic leukemia (M7). 249 48

We studied peripheral blood lymphocytes (PBL) of eight B chronic lymphocytic leukemia (CLL) patients for the expression of the human leucocyte antigens, HLA-DR and HLA-DQ. Cell surface expression of HLA class II epitopes was analyzed by fluorescent activated cell sorter (FACS) using three monomorphic anti-HLA class II monoclonal antibodies (mAb) specific for DR (D1.12) and DQ (TU22, L2) and a polymorphic anti-DQ (G2A5). The DR and DQ molecules were characterized by two-dimensional gel electrophoresis (2D-PAGE) of the specific immunoprecipitates from biosynthetically labeled cells. DR, DQ specific probes were used to characterize the class II transcripts of the corresponding genes. The data obtained with immunofluorescence disclosed two distinct patterns of HLA class II expression leading to two cell surface phenotypes: (DR+DQ+) and (DR+DQ-). In all cases the cells expressed normal amounts of HLA-DR gene products in terms of mRNA. DR cell surface determinants were present in more than 80% of cells in every sample. By 2-D gel analysis DR proteins disclosed the normal classical pattern associating the alpha, beta, and invariant chain gamma with normal level of biosynthesis for alpha and gamma but decreased biosynthesis for one of the beta gene products. Moreover, the three chains demonstrated defect in glycosylation process. In half of the cases studied the cells lacked DQ molecules at the cell surface. DQ alpha and DQ beta transcripts were detected in all cases, although the amount was extremely low in one case. DQ proteins were variable in the DQ+ phenotype and absent in the DQ- one. Interestingly, TPA and rIFN gamma treatment could restore normal glycosylation process of the DR isotype and increase biosynthesis of DQ alpha and beta chains. Those combined results support the view that transcriptional, post-transcriptional, and posttranslational mechanisms underlie the heterogeneity of class II expression observed in CLL. Moreover, 2-D gel analysis may be an invaluable tool for the analysis of the biosynthetic process of class II molecules.
Leukemia 1989 May
PMID:HLA-DR and DQ antigens in chronic lymphocytic leukemia: dissociation of expression revealed by cell surface, protein, and mRNA studies. 249 83

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.
 ...
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.
Leukemia 1989 Jun
PMID:Expression of the myeloperoxidase gene in acute and chronic myeloid leukemias: relationship to the expression of cell cycle-related genes. 254

A long term cultured cell line (c-WRT-7) was successfully established from the transplantable rat myelomonocytic leukemia (WRT-7). Analysis of cell surface markers and phagocytic properties of c-WRT-7 cell showed that about 10% of c-WRT-7 cells differentiated spontaneously from blastic cells to macrophage-like cells in the culture. The differentiation of c-WRT-7 cells was markedly enhanced by in vitro treatment of cells with lipopolysaccharide (LPS), phorbol ester (TPA) and retinoic acid. Of these chemicals, LPS was the strongest enhancer of the differentiation of c-WRT-7 cells over the wide range of doses tested. The transplantation of c-WRT-7 cells into the peritoneal cavity of WKA rat (derived host) proved lethal with a significant increase of blastic tumor cells. Conversely, in SHR rat, which has a common major histocompatibility antigen with WKA rat (RT-1k), although the transplanted c-WRT-7 cells grew well as was observed in WKA rat, increased blastic cells were replaced by the differentiated macrophage-like cells and finally were rejected. Furthermore, the increasing differentiation activity of c-WRT-7 cells in vitro was detected in the peritoneal fluid and serum of SHR rat accompanied by the transplantation of c-WRT-7 cells. This is significantly different from the case of the Fischer rat with a different major histocompatibility antigen (RT-1l) in which transplanted c-WRT-7 cells scarcely grew and were rejected immediately.
 ...
PMID:[Establishment of rat myelomonocytic leukemia cell line (c-WRT-7)--induction of differentiation and transplantation into syngeneic and non-syngeneic rats]. 260 51

Induction of differentiation in B lymphoma/leukemia cells with interleukins was compared with differentiation induced by phorbol ester (TPA) and pokeweed mitogen (PWM) or by 8-bromo-guanosine. Both cell surface changes and monoclonal immunoglobulin (Ig) secretion were followed as markers of differentiation. The results indicate great similarity in the differentiation patterns induced by interleukin-1 (IL-1), interleukin-2 (IL-2), and interleukin-4 (IL-4), with regard to Ig secretion and changes in surface markers. Induction of Ig secretion and surface marker changes by 8-bromo-guanosine was similar to that induced by TPA and PWM; however, for some markers, cell surface changes induced by TPA and PWM or by 8-bromo-guanosine were quite different from those induced by the three interleukins tested. Whereas all three interleukins stimulated the expression of CD5, PWM and TPA and 8-bromo-guanosine substantially decreased CD5 expression on B lymphoma cells. Differences were also observed in the effect on the expression of surface Ig and on the expression of CD19 and CD20. Interestingly, the three interleukins tested and 8-bromo-guanosine induced differentiation and Ig secretion within 24 to 48 hours with no prior activation by B-cell activators, such as anti-surface Ig antibody. These results suggest that leukemic B cells are arrested at a point distal to activation and first cell division. Moreover, the similarity in Ig secretion and surface changes induced by TPA and PWM or 8-bromo-guanosine suggest a similar pathway; however, this pathway is different from the differentiation signal induced by the three interleukins.
 ...
PMID:Induction of surface marker changes and monoclonal idiotypic immunoglobulin secretion in lymphoma/leukemia cells: comparative study with interleukin-1, interleukin-2, interleukin-4, 8-bromo-guanosine, pokeweed mitogen, and tetradecanoyl phorbol-13-acetate. 261 Sep 49


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