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)

The nm23-H1 gene is regarded as a human homologue of the mouse nm23 gene, which was expressed in a non-metastatic subline of mouse melanoma K-1735. The expression levels of nm23-H1 mRNA and the levels of protein during induced differentiation of human leukemia cell lines were analysed. mRNA levels of the megakaryoblastic leukemia line MEG-01, which were induced to differentiate into megakaryocyte by TPA, decreased rapidly from 2 days after the start of treatment and became almost undetectable at day 4. Similar down-regulation of nm23-H1 mRNA was also observed in the induced differentiation of the promyelocytic leukemia line HL-60 by TPA, or DMSO into monocyte-macrophage lineage or granulocytes, respectively. The amount of Nm23-H1 protein was analysed by Western immuno-blot analysis using mouse antiserum raised against a recombinant fusion protein with glutathione S-transferase. The amount of Nm23-H1 protein also decreased during the induced differentiation of these leukemia cell lines. On the other hand, in the differentiation of the erythroleukemia line K562 by hemin, levels of both mRNA and protein of Nm23-H1 elevated transiently, then reduced to the original level. When MEG-01 and K562 were stably transfected with nm23-H1 cDNA, MEG-01 transfectants showed reduced sensitivity to the induction of differentiation, whereas K562 transfectants were better induced to synthesize hemoglobin than controls. These findings suggest the possibility that Nm23-H1 protein plays an important role to maintain the proliferation of immature leukemic cells in MEG-01 and HL-60, but it may also play a role in the early stage of K562 differentiation, possibly in the different manner.
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PMID:Alteration of nm23 gene expression during the induced differentiation of human leukemia cell lines. 805 9

Influence of sera of 15 patients with acute lymphoblastic leukaemia (ALL) and 28 with acute myeloblastic leukaemia (AML) on proliferation and differentiation of human leukaemic cell lines K-562 and HL-60 in a 3 days liquid culture was examined. Differentiation of K-562 cells was measured by the percentage of cells synthesizing Hb, and HL-60 cells by the percentage of cells with positive NBT test and positive NSE activity. Additionally the influence of differentiation inducers such as hemin for K-562 and DMSO and TPA for HL-60 was examined. It has been found that sera of patients with ALL and AML inhibit the proliferation of K-562 and HL-60 cells, induce the differentiation of K-562 cells, but inhibit the induction of differentiation by hemin. The sera of the examined patients inhibit the differentiation of HL-60 into granulocytes and monocytes, but do not affect the differentiation induced with DMSO and TPA.
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PMID:[Influence of patients' sera in acute leukemia on proliferation and differentiation of K-562 and HL-60 cells in liquid culture]. 806 89

The molecular basis of commitment and differentiation of hematopoietic cells remain poorly understood at the genetic level. Among putative candidates involved in these processes are homeoproteins, a large family of transcription factors which play a major role during development. Using a strategy based on the polymerase chain reaction (PCR) we have isolated nine different Antennapedia-like homeobox (HOX) genes from purified human hematopoietic precursors. Their expression patterns, analyzed with a panel of leukemia-derived cell lines representing various blood cells phenotypes, appears to be lineage-restricted. Extending our study to all the known members of the HOX 1 and HOX 2 clusters, we found that HOX 1 genes are predominantly detected within cell of myelomonocytic origin whereas HOX 2 genes transcripts are principally expressed in erythro-megakaryocytic cell lines. Furthermore, we have observed that the expression of three HOX 1 genes within B lymphoid lineages is stage-related and that the expression of several of them is switched off during TPA-induced differentiation of KG1 and U937 cells. These observations support the idea that homeoproteins could be regulators of lineage determination during hematopoiesis.
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PMID:[Homeoproteins: participation in hematopoietic processes?]. 810 52

Human T cells require two discrete signals to initiate their proliferation. In Jurkat T cells the first signal can be provided by the phorbol ester TPA and the second by the calcium ionophore A23187. We have isolated a cDNA from Jurkat T cells representing mRNA induced by TPA but inhibited by simultaneous treatment of the cells with antibody, lectin, or A23187. Sequencing revealed identity of the Jurkat clone to a cDNA, termed ETR101, recently isolated from HL60 promyelocytic leukaemia cells and shown to be an immediate early gene expressed upon TPA stimulation of these cells [Shimizu et al.: J Biol Chem 266:12157, 1991]. The gene is also induced very rapidly upon TPA treatment of Jurkat cells and is superinduced by co-treatment with cycloheximide. The predicted amino acid sequence encoded by ETR101 has weak homology to JunB and JunD, therefore it is of some interest that these three genes share the chromosomal localization, 19p13.2. The divergent effects of TPA treatment upon cell proliferation and differentiation in different circumstances allow some speculation about a possible role for the ETR101 gene product upon cellular differentiation.
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PMID:Phorbol ester-induced transcription of an immediate-early response gene by human T cells is inhibited by co-treatment with calcium ionophore. 817 88

In the human leukemic HL-60 cell line, we have reported previously that monocytic/macrophage-like differentiation induced by TPA (12-O-tetradecanoylphorbol-13-acetate) was associated with a decreased sensitivity to various apoptosis-inducing stimuli (Solary, Bertrand, Pommier, Blood 1993; 81:1359-1368). In the present study, we studied further the effects of TPA alone on the induction of apoptosis in HL-60 cells. Based on morphology by electron microscopy, identification of internucleosomal DNA cleavage by gel electrophoresis and quantitation of DNA fragmentation by a filter binding assay, we observed that neither morphologic changes nor DNA damage were identified in TPA-differentiated HL-60 cells as long as they kept the adherent phenotype characteristic of this differentiation pathway. However, adherent TPA-treated HL-60 cells that secondarily detached from the flask demonstrated internucleosomal DNA fragmentation associated with morphologic changes characteristic of apoptosis. Similarly, HL-60 cells that never became adherent after TPA treatment underwent rapid apoptosis. Granulocytic differentiation by retinoic acid (RA) treatment also induced apoptosis although more slowly. Interestingly, in both TPA- and RA-treated cells, apoptotic bodies appeared to be phagocytosed by differentiated cells from the same lineage. Internucleosomal DNA fragmentation was also identified in HL-60 cells induced to differentiate by sodium butyrate and dimethylsulfoxide treatment, suggesting that apoptosis could be the common mode of death of terminally differentiated HL-60 cells.
Leukemia 1994 May
PMID:Apoptosis of human leukemic HL-60 cells induced to differentiate by phorbol ester treatment. 818 36

Annexin VIII is a calcium- and phospholipid-binding protein with anticoagulant activity. Annexin VIII mRNA was found to be specifically expressed in acute promyelocytic leukemia (APL) cells; it was not found in other types of acute myeloid leukemia (AML) nor in lymphoid malignancies. Using Northern blot analysis we investigated annexin VIII expression in 142 continuous human leukemia and lymphoma cell lines at the mRNA level. While the only APL cell line, NB-4, was indeed positive, other cell lines also displayed annexin VIII mRNA: 4/22 myeloid cell lines, 8/23 monocytic cell lines, 2/8 megakaryoblastic cell lines, 5/26 lymphoma-derived cell lines, 2/10 myeloma cell lines and 1/44 lymphoid leukemia cell lines. The strongest expression was seen in NB-4 and in the Hodgkin's disease derived cell line HDLM-2. Treatment of NB-4 cells with all-trans retinoic acid (ATRA) or the phorbol ester TPA induced terminal differentiation and down-regulated annexin VIII mRNA expression rapidly within a few hours; vitamin D3 was ineffective in this regard; the protein kinase C activator Bryostatin 1 up-regulated the expression. A panel of initially negative cell lines could not be induced by any of these biomodulators to transcribe annexin VIII. The half-life (T1/2) of annexin VIII mRNA was about 3-4 h using actinomycin D as transcription inhibitor. Treatment with ATRA or TPA prior to exposure to actinomycin shortened the T1/2 to 2 h while Bryostatin 1 extended it to 6h. As 21/141 non-APL cell lines were positive, annexin VIII cannot be used as a marker gene for APL cells; however, it might be associated with myelomonocytic or erythro-megakaryoblastic precursor cells. Annexin VIII gene expression might play a unique role in the proliferation and/or differentiation of leukemic cells and could be associated with the particular abnormal hemostasis of some leukemias.
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PMID:Expression and modulation of annexin VIII in human leukemia-lymphoma cell lines. 823 Dec 35

Earlier work demonstrated that the Myb-Ets fusion protein of E26 avian leukemia virus induces the proliferation of multipotent hematopoietic progenitors (MEPs). These progenitors differentiate spontaneously at low frequencies along the erythroid lineage, and following the introduction of kinase/ras-type oncogenes or treatment with TPA, they are induced to differentiate along the myelomonocytic and eosinophilic lineages. Here, we show that the ts1.1 mutant of E26 encodes an Ets DNA-binding domain that is both defective and thermolabile for binding of specific DNA sequences. Correlating with this, ts1.1 MEP colonies transformed at the permissive temperature exhibit elevated levels of erythroid cells and eosinophils, whereas at the nonpermissive temperature they are induced to differentiate along the erythroid and myelomonocytic lineages and, to a lesser extent, along the eosinophil lineage. Induction of the former two lineages cannot be separated by pulse shift experiments and is essentially completed 2.5 days after temperature shift. Our results indicate that the Ets portion of the Myb-Ets fusion protein inhibits the lineage commitment of multipotent hematopoietic progenitors, probably via binding to regulatory DNA sequences of specific target genes.
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PMID:A functional Ets DNA-binding domain is required to maintain multipotency of hematopoietic progenitors transformed by Myb-Ets. 828 26

The proto-oncogene c-met encodes a heterodimeric (alpha, beta) tyrosine kinase receptor which binds the hepatocyte growth factor (HGF). Recently, overexpression of the Met/HGF receptor gene has been detected in fresh samples of carcinomas and in epithelial tumor cell lines but not in cell lines derived from human leukemia and lymphoma. Our analysis of 50 primary samples of human leukemia and lymphoma and 23 hematopoietic cell lines revealed expression of mRNA and protein of the met/HGF receptor in 6 out of the 73 hematopoietic tumor samples analyzed. Four of the six samples positive for expression of the Met/HGF receptor gene were derived from patients with Hodgkin's disease. In addition, in one Burkitt's lymphoma cell line and in one acute myeloid leukemia (AML), expression of the Met/HGF receptor gene was detected. In normal unstimulated lymphocytes, granulocytes or monocytes we did not find expression of the Met/HGF receptor gene. Upon stimulation with the phorbol ester TPA we detected a weak expression of Met/HGF receptor specific transcripts of 9.0 kb in peripheral blood mononuclear cells of a healthy donor. Cytogenetic analyses of three of the four cell lines which express the Met/HGF receptor gene revealed structural or numerical abnormalities of the long arm of chromosome 7, where the Met/HGFR gene is located, in each of the three cell lines analyzed. In one of these cell lines (L540) the Met/HGFR gene is translocated to a marker chromosome. Southern blot and pulsed field gel electrophoresis experiments did not show any rearrangement in a region of 600 kb around the Met/HGF receptor gene excluding an activation of Met/HGFR by a TPR/Met oncogenic rearrangement as described for MNNG-HOS cells and for some gastric tumors. Our data indicate that the Met/HGFR gene is deregulated in a few cases of human leukemia, Burkitt's lymphoma and Hodgkin's disease possibly by chromosomal rearrangements resulting in an overexpression of the normal Met/HGF receptor mRNA and protein without formation of a hybrid gene.
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PMID:The Met/hepatocyte growth factor receptor (HGFR) gene is overexpressed in some cases of human leukemia and lymphoma. 828 71

The CD45 protein is a transmembrane tyrosine phosphatase that is required for normal T and B cell receptor-mediated signaling. In order to study the function of this phosphatase in mast cells, we have isolated a CD45-deficient variant from the rat basophilic leukemia cell line (RBL-2H3), a tumor analog of mucosal mast cells. The secretory response as well as the inositol 1,4,5-triphosphate (InsP3) formation to Fc epsilon RI and ionophore stimuli were similar in the RBL-2H3 cell line and its derived CD45-deficient subpopulation. However, pretreatment with the phorbol ester TPA, which directly activates protein kinase C (PKC), caused a marked increase in mediator release and InsP3 production in the CD45-deficient variant compared to the parental RBL-2H3 cells. These findings suggest that CD45 might directly or indirectly modify the activity of PKC or the InsP3-dephosphorylating phosphatase.
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PMID:CD45-deficient RBL-2H3 cells. Cellular response to Fc epsilon R- and ionophore-induced stimulation. 830 Jan 59

The effects of bryostatin 1 (Bryo 1), a protein kinase C (PKC) activator, on proliferation, differentiation and macromolecular synthesis were investigated in the two cell lines EHEB and JVM-2, established from patients with chronic B-cell leukemia. Treatment with Bryo 1 inhibited the proliferation, DNA and RNA synthesis in a time- and dose-dependent fashion. The cells differentiated along the B-cell pathway to plasmacytoid cells as judged by morphological examination and increased their production and secretion of immunoglobulins. c-myc mRNA expression was induced in both cell lines. The phorbol ester TPA, a pharmacological PKC activator, had similar differentiation-inducing effects. The biomodulators failed to induce significant alterations in the cell surface marker profile. Except for their surface markers, all parameters studied were more strongly altered in JVM-2 than in EHEB cells. JVM-2 was established from a patient with B-prolymphocytic leukemia (PLL), whereas EHEB originated from a case of B-chronic lymphocytic leukemia (CLL). These data support the notion that PLL cells appear to be activated B-cells, in contrast to the rather quiescent CLL cells. Since Bryo 1 lacks tumor-promoting activity, this naturally occurring compound, extracted from marine animals, has a potential role in the therapy of B-cell neoplasms as a differentiating agent.
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PMID:Induction of differentiation of B-cell leukemia cell lines JVM-2 and EHEB by bryostatin 1. 837 21


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