Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ultrastructural, flow cytometric, and molecular studies were performed on leukemia cells from bone marrow and pleural effusion of a 6-year-old boy diagnosed with undifferentiated (MO) leukemia, using routine histology and immunostains at diagnosis and relapse. Ultrastructurally, surface and/or intracellular ferritin particles were present on or in some blasts and the majority of blasts contained identifiable acid ferrocyanide reactive inorganic iron comparable to that seen in normal early erythroblasts. The cells lacked other evidence of differentiation, including diaminobenzidine-reactive or immunoreactive hemoglobin. Flow cytometric analysis of malignant cells showed a lack of lymphoid or myeloid markers. Anti-transferrin receptor antibody was positive on 93% of cells and antibody to glycophorin A reacted with 23% of cells. RNA blot analysis of leukemia cells with myeloperoxidase (MPO) showed an absence of appreciable levels of MPO mRNA. Chromosome analysis showed 51,XY, t(1;16)(p31;q24), +6, +10, +15, +19, +21. The oncogene c-myb, which is specifically expressed and regulated in hematopoietic cells and produces a DNA-binding protein responsible for myeloid differentiation, was found to be duplicated in the patient's tumor cells. Expression of c-jun, N-ras, c-myc, and p53 was normal. The data indicate that the malignant cells in this patient are of early erythroid lineage at diagnosis and relapse and that classification of cell lineage can be enhanced by ultrastructural Prussian blue staining. The failure of this otherwise undifferentiated leukemia to express or evolve into a myeloid phenotype is biologically and clinically distinct from previously described cases of erythroid and myeloid leukemia and may represent a previously unidentified phenotype which should be included in the spectrum of 'undifferentiated' childhood leukemia.
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PMID:Childhood undifferentiated leukemia with early erythroid markers and c-myb duplication. 170 34

Murine erythroleukemia cells rendered deficient in cAMP-dependent protein kinase (A-kinase) activity by gene transfection are severely impaired in hexamethylene bisacetamide (HMBA)-induced differentiation (Pilz, R. B., Eigenthaler, M., and Boss, G. R. (1992) J. Biol. Chem. 267, 16161-16167). We now demonstrate that the A-kinase-deficient cells produce hemoglobin normally in response to exogenous hemin and that the heme precursor delta-aminolevulinate (delta-ALA) significantly increases HMBA-induced synthesis of heme and globin chains in these cells; these data suggest that impaired heme synthesis is at least partially responsible for the cells' deficient hemoglobin synthesis. HMBA-induced expression of the erythroid-specific delta-ALA synthetase, porphobilinogen deaminase, and beta-globin mRNAs was less in A-kinase-deficient cells than in parental cells and was reduced in proportion to the cells' residual A-kinase activity; relative transcription rates of these genes were reduced concordantly. Impaired expression of these three erythroid-specific genes was a feature of many independently-derived A-kinase-deficient clones, and normal expression was found in transfectants with normal A-kinase activity. The A-kinase-deficient cells did not exhibit a generalized defect in gene regulation since mRNA expression and transcription rates of H- and L-ferritin, c-myc, c-myb, and several housekeeping enzymes were similar in HMBA-treated parental and A-kinase-deficient cells. Our data suggest that A-kinase may be involved in regulating genes with erythroid-specific promoters and provide further evidence for heme as a regulator of globin chain synthesis.
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PMID:Impaired erythroid-specific gene expression in cAMP-dependent protein kinase-deficient murine erythroleukemia cells. 837 86

We previously have shown that the zinc finger transcription factor Egr-1 blocked granulocytic differentiation of HL-60 cells, restricting differentiation along the monocytic lineage. Egr-1 also was observed to block granulocyte colony-stimulating factor (G-CSF)-induced differentiation of interleukin-3 (IL-3)-dependent 32Dcl3 hematopoietic precursor cells, endowing the cells with the ability to be induced by granulocyte-macrophage colony-stimulating factor (GM-CSF) for terminal differentiation along the macrophage lineage. To better understand the function of Egr-1 as a positive modulator of monocytic differentiation, in this work we have studied the effect of ectopic expression of Egr-1 on the murine myeloblastic leukemic cell line M1, which is induced for differentiation by the physiological inducer IL-6. It is shown that, unlike in HL-60 and 32Dcl3 cells, ectopic expression of Egr-1 in M1 cells resulted in activation of the macrophage differentiation program in the absence of differentiation inducer. This included the appearance of morphologically differentiated cells, decreased growth rate in mass culture, and cloning efficiency in soft agar, and expression of endogenous c-myb and c-myc mRNAs was markedly downregulated. Untreated M1Egr-1 cells also exhibited cell adherence, expression of Fc and C3 receptors, and upregulation of the myeloid differentiation primary response genes c-Jun, junD, and junB and the late genetic markers ferritin light-chain and lysozyme. Ectopic expression of Egr-1 in M1 cells also dramatically increased the sensitivity of the cells for IL-6-induced differentiation, allowed a higher proportion of M1 cells to become terminally differentiated under conditions of optimal stimulation for differentiation, and decreased M1 leukemogenicity in vivo. These findings demonstrate that the functions of Egr-1 as a positive modulator of macrophage differentiation vary, depending on the state of lineage commitment for differentiation of the hematopoietic cell type.
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PMID:The zinc finger transcription factor Egr-1 activates macrophage differentiation in M1 myeloblastic leukemia cells. 973 Oct 53