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

In a prospective study, 16 patients with chronic B-lymphocytic leukaemia (CLL) were repeatedly investigated for clinical and laboratory signs of disease activity during a period of 18 months. The leukaemic cells were induced to differentiate in vitro using a phorbol ester, TPA. Two differentiation-associated properties of the tumour cells, i.e. the amount of cytoplasmic immunoglobulin (C-IgM) and the increased sensitivity to lysis by natural killer (NK) cells, were expressed in parallel and both parameters were positively correlated with the clinical activity of leukaemia. Phorbol ester-induced phenotypic changes of the leukaemic cells may therefore be used for the in vitro monitoring of disease activity in CLL. The present markers may, in addition, be useful in molecular analysis of B cell differentiation.
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PMID:Natural killer (NK) cell sensitivity of phorbol ester-differentiated tumour cells correlates with disease activity in chronic B-lymphocytic leukaemia. 698 24

Normal human B cells and leukaemic B-cell populations in common-type CLL undergo sequential shifts in proportions of the three B-cell subsets, defined by expression of mouse erythrocyte receptors R1 and R2, during TPA-induced differentiation to plasmacytoid cells in vitro, suggesting that the B-cell differentiation pathway is R1 +R2+ leads to R1 -R2+ leads to R1 -R2- leads to immature plasmacyte. Maturation of the less common type of CLL with a predominance of R1 -R2+ type cell was in agreement with this model. Changes in Fc gamma, Fc mu and C' receptors were also observed during maturation. A model of human B-cell maturation is presented on which common sites of blockage in leukaemia can be located.
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PMID:Human B-lymphocyte maturation sequence revealed by TPA-induced differentiation of leukaemic cells. 698 91

The induction of p53 by doxorubicin in normal human fibroblasts was completely reverted by TPA, a phorbol ester. A ts-p53 mutant protein which is ineffective at 37 degrees C, but behaves in a wild-type fashion at 32 degrees C, was overexpressed in the p53-null human leukemia cell line K562. Wild-type-p53 overexpression induced apoptosis, whereas TPA protected K562 cells from this phenomena. By analogy with the observed human fibroblasts, TPA was found to decrease p53 amount. The TPA-dependent down-regulation of p53 could explain the chromosomal gross alterations typical of cells subjected to a chronic TPA treatment, alterations also found in cells defective for p53 function.
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PMID:Phorbol esters attenuate the expression of p53 in cells treated with doxorubicin and protect TS-P53/K562 from apoptosis. 748 3

Tax of human T-cell leukemia virus type I (HTLV-I) activates transcription at a CArG box of various immediate early genes such as the proto-oncogene c-fos. To do this, Tax does not directly bind to the CArG box, but instead binds to the CArG binding factor SRF. In this study, we investigated the domain of SRF required for the activation by Tax and studied the role of this domain on transcriptional regulation at the CArG box. Using a fusion protein of SRF with a yeast transcription factor GAL4, the 14 amino acid (aa) portion (aa 422-435) of SRF was identified as the domain required for Tax activation [Tax-responsive region of SRF (TRRS)]. By means of a two hybrid system, we showed that TRRS was essential for the interaction of SRF with Tax in vivo. The over-expression of SRF with a deletion of TRRS inhibited the Tax activation at the CArG box. Thus, TRRS is the domain of SRF that is essential for Tax activation at the CArG box. Unlike to Tax activation, TRRS was not required for TPA (12-o-tetradecanoylphobol-13-acetate) induction at the CArG box, but a TRRS deletion enhanced the basal activity at the CArG box both under serum-starved and TPA-stimulated conditions. These results suggest that TRRS negatively regulates the transcriptional activation function of SRF, and consequently contributes to the low basal activity at the CArG box before TPA induction.
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PMID:Identification of the Tax interaction region of serum response factor that mediates the aberrant induction of immediate early genes through CArG boxes by HTLV-I Tax. 762 33

One of 8 to 12 pre-B ALL cells co-express CD13 and CD33 antigens, but such blasts do not express myeloperoxidase (MPO) even on electronmicroscopy or mRNA. MPO+ pre-B ALL is extremely rare (1/50-1/100), however a cell-line (Tahr87) was established in culture. In contrast, T-lineage blasts express CD13/33 antigens regularly in the pro-thymic stage (CD7+ 5+ 2+ 3- 4- 8- or more immature), and a limited expression of MPO is rather commonly detected particularly in recurrences. The co-expression of CD3 epsilon/MPO or CD3 epsilon/delta/MPO mRNA has been demonstrated. Thus, the regulation of MPO expression is of utmost importance in interpreting the phenotypes of leukemia/lymphoma. While testing the effects of several cytokines on MPO expression, IFN-gamma was found to suppress the gene expression of MPO in HL60 cells. This suppression was not accompanied by differentiation, termination of proliferation or reduction of cytochemical MPO+ cells, and was reversible. Among 22 cases of M1 AML blasts, 8 cases were HLA-DR(-). DR antigen was induced by the presence of a mixture of IFN-gamma, TNF-alpha and TPA in 4 cases, but not in the other 4 cases. The blasts of the latter 4 cases were always CD34(-), CD7(-) and CD45RA-/RO+, and constituted a distinct M1 subset which has not previously been reported.
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PMID:[Cytokine in phenotypic analysis of leukemia/lymphoma: suppression of gene expression of myeloperoxidase by IFN-gamma and subset of AML M1 defined by CD45RO+/RA-, CD7(-), CD34(-) and non-inducible HLA-DR antigen]. 768 32

Retinoic acid (RA) is capable of inducing the differentiation of various myelomonocytic cell lines. During this differentiation process, the levels of c-myb expression decline, suggesting that the RA receptor (RAR) may act in part by down-regulating this proto-oncogene. We have now investigated whether the RAR can also inhibit the function of Myb proteins themselves. We have found that transcriptional activation of a Myb-responsive reporter gene can be inhibited by RA in a human monocytic cell line. This inhibition could not be overcome by the expression of exogenous Myb. The RAR did not interfere with DNA binding by Myb proteins in vitro, suggesting that the functional inhibition occurs at the level of transcriptional activation. To determine the biological relevance of the inhibition of Myb proteins by the RAR, we have used v-myb-transformed monoblasts. These cells differentiate into macrophages in the presence of phorbol ester (tetradecanoyl phorbol acetate [TPA]) but are normally unresponsive to RA treatment. The introduction of an inducible, exogenous RAR alpha into v-myb-transformed monoblasts permitted an RA-dependent differentiation into macrophage-like cells similar to those induced by TPA. These results demonstrate that transformation by v-myb is recessive to RAR alpha and imply that many types of non-RA-responsive leukemia cells may become responsive following the introduction of the RAR.
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PMID:Retinoic acid receptor alpha suppresses transformation by v-myb. 773 32

We have already established a human leukemia sub-line resistant to the growth-inhibitory effect of TPA (12-O-tetradecanoylphorbol 13-acetate) (K562/TPA) derived from K562. K562/TPA was found to be a non-P-glycoprotein-mediated multidrug-resistant cell line, in which intracellular drug accumulation was not reduced. In K562/TPA, adriamycin (ADM) was distributed mainly in the cytoplasm and was scarcely observed in the nucleus. We determined the relative levels of multidrug-resistance-associated protein (MRP), which was recently identified as the novel transporter. The relative levels of MRP in K562/TPA were the same as in K562. Although the catalytic activity of K562/TPA topoisomerase II was about half that of the parental cells, resistance to other drugs could not be explained by topoisomerase-II activity. To elucidate the mechanism of drug resistance in K562/TPA, we tried to find chemicals that would reverse the drug resistance. Tyrosine-kinase inhibitors enhanced the cytotoxicity of anti-neoplastic drugs against K562/TPA. Therefore we examined the modification of nuclear ADM accumulation in K562/TPA by one of these tyrosine-kinase inhibitors, genistein. Although the amount of ADM was decreased in the nuclei of K562/TPA cells, it was significantly increased after incubation in the presence of genistein. The formation of DNA single-strand breaks by ADM, etoposide, and ACNU was significantly lower in K562/TPA than in K562, but was significantly increased in the presence of genistein. These results suggest that genistein could overcome drug resistance by enhancing the accumulation of drug into the nuclear fraction of K562/TPA.
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PMID:Reversal of multidrug resistance by tyrosine-kinase inhibitors in a non-P-glycoprotein-mediated multidrug-resistant cell line. 790 94

Flow cytometric and immunochemical studies performed with the CD66/67 panel antibodies from the Vth International Workshop on Leukocyte Antigens allowed to subdivide these antibodies into five groups, according to the molecular weights of polypeptides recognized by these antibodies on pooled healthy donor granulocytes. Although some monoclonal antibodies recognized either 95-110 kDa, or 160-180 kDa polypeptides, majority of the examined antibodies reacted with epitopes shared by both 95-110 kDa and 160-180 kDa polypeptides. Differential TPA-induced modulation of recognized antigens was observed with HL-60 and U-937 leukemia/lymphoma cell lines.
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PMID:Myeloid activation antigen CD66/67: immunochemical and immunocytometric characterization with the Vth workshop monoclonal antibodies. 793 79

We present the clinical and immunological features of a rare case of chronic lymphoid leukaemia with lymphoplasmacytoid morphology. The patient was first admitted suffering from weakness, pallor, dyspnoea, marked splenomegaly, hepatomegaly and systemic lymphadenopathy and panhypogammaglobulinaemia. White blood cell count revealed important leukocytosis (220 x 10(9) WBC/l) with 2% neutrophils and 98% lymphoid cells showing lymphoplasmacytoid features, while lymphoid cells of identical morphology severely infiltrated the bone marrow and lymph nodes. The disease, initially controlled by non aggressive chemotherapy over a period of 30 months, later evolved to a clinical and haematological picture suggestive of Richter's syndrome. Immunophenotyping of the leukaemic cells demonstrated a monoclonal expansion of B-cells bearing surface markers of typical CLL (CD5, CD19, CD20, CD21, CD22, CD23, CD24, CD40 and low density IgM+IgD/kappa) and also the CD11c and CD38 antigens. A proportion of these cells expressed activation markers (CD25, CD69 and CD71). Following in vitro activation with TPA or PWM, the cells responded by weak incorporation of 3H-TdR but failed to secrete immunoglobulins. These findings confirm the broad morphological, phenotypical and clinical spectrum of chronic lymphoid leukaemias.
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PMID:Monoclonal expansion of immunoglobulin not-secreting CD5+ CD11c+ CD38+ B-cells in a rare case of chronic lymphoplasmacytoid leukaemia. 797 Dec 44

In the present paper, we investigated the pathophysiological implication of TGF-beta from megakaryocytes or megakaryoblasts in the development of myelofibrosis. In the bone marrow of myelofibrosis, proliferation of megakaryocytes is often noticed. We therefore investigated the TGF-beta expression in the bone marrow megakaryocytes from 12 chronic myeloproliferative disorder patients with myelofibrosis by immunohistochemical analysis. About all the specimen showed strong positivity for TGF-beta. In order to examine whether megakaryoblasts produce TGF-beta, we then measured TGF-beta activity in the conditioned medium (CM) of megakaryoblasts from a patient with acute megakaryoblastic leukemia who had profound myelofibrosis. The CM showed strong collagen synthesis stimulating activity which was nullified by addition of anti TGF-beta antibody. Since TGF-beta exists as latent form in platelets, TGF-beta was considered to be altered from active to latent form during megakaryocytes differentiation. In this context, MEG-01, a megakaryoblastic cell line which produces active TGF-beta was underwent differentiation to produce platelet-like bleb with TPA treatment. During the differentiation, MEG-01 showed the decrease of active TGF-beta production and increase of latent TGF-beta together with the production of LTBP. These results suggest that megakaryoblasts produce active TGF-beta and may may cause myelofibrosis, while more differentiated megakaryocytes produce latent TGF-beta. Mechanism by which megakaryoblast escape from negative autocrine of active TGF-beta was also investigated. MEG-01 was found to express mutated p53 which is considered to be responsible for impaired signal transduction of TGF-beta.
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PMID:[TGF-beta and platelet]. 802 82


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