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 relationship between growth rate and various parameters of the heme biosynthetic pathway was studied in two cell lines of rat fibroblasts (REabl-1 and REabl-3) transfected with v-abl oncogene, coded by the Abelson murine leukemia virus, and subjected to glucocorticoid dependent transformation. In the REabl-1 cell line, whose growth rate was only slightly affected by dexamethasone (DX), almost no change was noticed either in heme content or in the enzymatic activities of aminolevulinate synthase (ALAS), porphobilinogen deaminase (PBGD), and ferrochelatase (FC) in the presence of various concentrations of DX. In the REabl-3 cell line, exhibiting a growth rate highly sensitive to DX, a significant reduction in intracellular heme concomitantly with decreases in ALAS and FC activities and a threefold increase in PBGD were noted. The fact that incubation with 10(-5)M hemin did not result in a decrease in ALAS activity raised the possibility that REabl cells lack a negative feedback control mechanism. The relationships between transformation, growth rate, and heme biosynthetic pathway are discussed.
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PMID:Transformation, growth rate, and the heme biosynthetic pathway in V-abl-transfected fibroblasts. 791 67

The biological activity of p53 in IW32 erythroleukemia cells was investigated. IW32 cells had no detectable levels of p53 mRNA and protein expression. By transfecting a temperature-sensitive mutant p53 cDNA, tsp53val135, into the cells, we have established several clones stably expressing the mutant p53 allele. At permissive temperature, these p53 transfectants were arrested in G1 phase and underwent apoptosis. Moreover, differentiation along the erythroid pathway was observed as evidenced by increased benzidine staining and mRNA expression of beta-globin and the erythroid-specific delta-aminolevulinic acid synthase (ALAS-E). Treatment of cells with protein tyrosine phosphatase inhibitor vanadate blocked the p53-induced differentiation, but not that of cell death or growth arrest. Increased protein tyrosine phosphatase activity as well as mRNA levels of PTPbeta2 and PTPepsilon could be observed by wildtype p53 overexpression. These results indicate that p53 induced multiple phenotypic consequences through separate signal pathways in IW32 erythroleukemia cells, and protein tyrosine phosphatase is required for the induced differentiation.
Leukemia 2000 Jul
PMID:Induction of IW32 erythroleukemia cell differentiation by p53 is dependent on protein tyrosine phosphatase. 1091 55

TEL/ETV6 accelerates erythroid differentiation in the murine erythroleukemia cell line. To clarify the effects of TEL on megakaryocytic maturation as well as erythroid differentiation, we chose the human leukemia cell line UT-7/GM that differentiates into the erythroid and megakaryocytic lineages by treatment with erythropoietin and thrombopoietin, respectively. Upon erythropoietin exposure, overexpressed TEL stimulated hemoglobin synthesis and accumulation of the erythroid differentiation-specific transcripts such as gamma-globin, delta-aminolevulinic acid synthase-erythroid, and erythropoietin receptor. Moreover, the glycophorin A(+)/glycoprotein IIb(-) fraction appeared more rapidly in the TEL-overexpressing cells. Interestingly, overexpression of TEL was associated with lower levels of the megakaryocytic maturation-specific glycoprotein IIb and platelet factor 4 transcripts under the treatment with thrombopoietin. Consistently, the glycophorin A(-)/glycoprotein IIb(+) fraction increased more slowly in the TEL-overexpressing cells. Finally, expression of endogenous TEL proteins in UT-7/GM cells was down-regulated following erythropoietin and thrombopoietin exposure. All these data suggest that TEL may decide the fate of human erythrocyte/megakaryocyte common progenitors to differentiate towards the erythroid lineage and against the megakaryocytic lineage.
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PMID:TEL/ETV6 accelerates erythroid differentiation and inhibits megakaryocytic maturation in a human leukemia cell line UT-7/GM. 1595 56

Protoporphyrin IX (PpIX), an immediate precursor of heme, is the main pigment resulting in the brown coloration of eggshell. The brownness and uniformity of the eggshell are important marketing considerations. In this study, 9 chickens laying darker brown shelled eggs and 9 chickens laying lighter brown shelled eggs were selected from 464 individually caged layers in a Rhode Island Red pureline. The PpIX contents were measured with a Microplate Reader at the wavelength of 412 nm and were compared in different tissues of the 2 groups. Although no significant difference in serum, bile, and excreta was found between the 2 groups, PpIX content in the shell gland and eggshell of the darker group was higher than in those of the lighter group, suggesting that PpIX was synthesized in the shell gland. We further determined the expression levels of 8 genes encoding enzymes involved in the heme synthesis and transport in the liver and shell gland at 6 h postoviposition by quantitative PCR. The results showed that expression of aminolevulinic acid synthase-1 (ALAS1) was higher in the liver of hens laying darker brown shelled eggs, whereas in the shell gland the expression levels of ALAS1, coproporphyrinogen oxidase (CPOX), ATP-binding cassette family members ABCB7 and ABCG2, and receptor for feline leukemia virus, subgroup C (FLVCR) were significantly higher in the hens laying darker brown shelled eggs. Our results demonstrated that hens laying darker brown shelled eggs could deposit more PpIX onto the eggshell and the brownness of the eggshell was dependent on the total quantity of PpIX in the eggshell. More heme was synthesized in the liver and shell gland of hens laying darker brown shelled eggs than those of hens laying lighter brown shelled eggs. High expression level of ABCG2 might facilitate the accumulation of PpIX in the shell gland.
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PMID:Comparison of protoporphyrin IX content and related gene expression in the tissues of chickens laying brown-shelled eggs. 2423 20

microRNAs (miRNAs) are involved in a variety of biological processes. The regulatory function and potential role of miRNAs targeting the mRNA of the 5'-aminolevulinate synthase 2 (ALAS2) in erythropoiesis were investigated in order to identify miRNAs which play a role in erythroid iron metabolism and differentiation. Firstly, the role of ALAS2 in erythroid differentiation and iron metabolism in human erythroid leukemia cells (K562) was confirmed by ALAS2 knockdown. Through a series of screening strategies and experimental validations, it was identified that hsa-miR-218 (miR-218) targets and represses the expression of ALAS2 by binding to the 3'-untranslated region (UTR). Overexpression of miR-218 repressed erythroid differentiation and altered iron metabolism in K562 cells similar to that seen in the ALAS2 knockdown in K562 cells. In addition to iron metabolism and erythroid differentiation, miR-218 was found to be responsible for a reduction in K562 cell growth. Taken together, our results show that miR-218 inhibits erythroid differentiation and alters iron metabolism by targeting ALAS2 in K562 cells.
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PMID:MiR-218 Inhibits Erythroid Differentiation and Alters Iron Metabolism by Targeting ALAS2 in K562 Cells. 2670 68