Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thy-1 (CDw90) is a phosphatidylinositol-anchored protein, and is expressed on human pluripotential hematopoietic stem cells. The expression pattern of this antigen on leukemia cells is still controversial. In this study, 72 adult patients with pre-B cell acute lymphoblastic leukemia (pre-B ALL) were examined for the expression pattern of Thy-1 by using indirect immunofluorescence and reversed transcription polymerase chain reaction (RT-PCR) methods. Twelve cases were judged positive on the basis of conventional immunophenotype criteria. Thirteen cases showed a weak clonal shift on the fluorogram, even though their positive percentages were from 6.7% to 14.9%. Thy-1 gene transcripts were detected in all of the 13 cases showing a weak clonal shift. The study of antibody binding capacity, which was calculated by the mean fluorescence intensity of the test sample on the basis of a calibration curve using standard beads, showed that cases with more than 150 sites/cell could be positive. Thy-1 positivity in pre-B ALL was not associated with the expression of B-cell differentiation antigens. Thy-1 expression was significantly higher in pre-B ALL cases with karyotypic abnormalities than in those with normal karyotype (p = 0.0071). The t(9;22) abnormality was found in 18 of the 25 Thy-1+ cases. Simultaneous expression of transcriptional factors, GATA-2 and SCL, was frequently detected in the Thy-1+ cases. bcr-abl and GATA-2 are thought to play important roles in the proliferation of immature hematopoietic cells. Indeed, cell-cycle analysis showed that the cell population in the S/G2/M phase of the present Thy-1+ cases was less than that in the Thy-1- cases (p = 0.001770). Our data suggest that Thy-1 expression indicates the proliferative status of the leukemia cells, not their phenotypic immaturity.
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PMID:Frequent expression of human Thy-1 antigen on pre-B cell acute lymphoblastic leukemia with t(9;22). 969 10

Erythropoietin (Epo) is essential for the later stages of erythropoiesis, acting to promote cell survival and proliferation, but its role in differentiation remains to be defined. The UT-7 cell line exhibits both erythroid and megakaryocytic characteristics and can be induced to differentiate along the erythroid pathway by Epo or the megakaryocytic pathway by phorbol myristic acetate. We have compared the effects of Epo and the chemical inducers, delta-aminolaevulinic acid (delta-ALA) and haemin on the differentiation capacity of UT-7 cells. Epo alone promoted relatively early events in erythroid maturation, without significant changes in haemoglobin production or morphology. GATA-2 and c-myb were down-regulated by Epo, and GATA-2 was further down-modulated by the inducers. Conversely, SCL expression was up-regulated by Epo and further increased by haemin and delta-ALA. Epo caused an increase in the proportion of cells expressing cell surface glycophorin A (GPA) and up-regulated beta- and gamma-globin by several fold. Both haemin and delta-ALA caused a de novo increase in alpha-globin expression as well as enhancing Epo-induced beta-globin expression, leading to a marked increase in haemoglobin production. These results suggest that haemoglobin production in UT-7 cells is limited by a deficiency of erythroid-specific aminolaevulinic acid synthase (ALAS-E) activity or globin synthesis as a consequence of their immaturity as a multipotential cell line.
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PMID:Erythroid gene expression is differentially regulated by erythropoietin, haemin and delta-aminolaevulinic acid in UT-7 cells. 1019 46

The aorta-gonads-mesonephros (AGM) region of the mouse embryo has been assigned as the origin of definitive hematopoiesis. The transcription factor GATA-2 has specific but unclarified roles in early hematopoiesis. To elucidate the expression profile of GATA-2, we prepared transgenic mouse lines containing the green fluorescent protein (GFP) gene driven by GATA-2 gene regulatory elements. We also prepared a mouse line in which GFP reporter sequences were inserted into the endogenous GATA-2 gene. Both mouse mutants expressed GFP in the early hematopoietic tissues. The CD45 antigen, a marker of hematopoietic cells, was expressed in a small fraction of transgene (TG)-derived GFP+ cells. The remaining TG-GFP+/CD45- cells were adherent to plastic and produced CD45+ hematopoietic cells abundantly when cultured in vitro. Exogenous expression of GATA-2 in TG-GFP+/CD45- cells from the AGM region inhibited their differentiation into CD45+ cells. Loss of GATA-2 function through the disruption of the GATA-2 locus enhanced the earlier emergence of CD45+ cells in the yolk sac of the 9.5-day conceptus. These results demonstrated that GATA-2 is expressed in the precursor of hematopoietic cells and works as a gatekeeper to preserve their immaturity. A reduction of GATA-2 expression or activity is required for the differentiation of precursors to hematopoietic cells.
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PMID:Expression and domain-specific function of GATA-2 during differentiation of the hematopoietic precursor cells in midgestation mouse embryos. 1268 39

GATA transcription factors have been shown to play important roles in hematopoiesis. GATA-2 is expressed in stem and progenitor cells, and has been speculated to control the proliferation and maintain the immaturity of these cells. To examine whether the function of GATA-2 is changeable according to the differentiation stage, we established GATA-2 overexpressing subclones of K562, which is a leukemic cell line committed to the erythroid lineage. Via an increase in the GATA-2 expression level, the expression levels of erythroid-specific genes including alpha-, beta-, and gamma-globin were increased compared to control cells, while the expression level of GATA-1 was unchanged. Expression of the transferrin receptor was also increased in GATA-2 overexpressing K562 cells when examined by flow cytometry. In addition, the heme content of GATA-2 overexpressing K562 cells was more than 2 times higher than control cells. Chromatin immunoprecipitation analysis showed that GATA-2 protein binding to the GATA element in alpha-globin LCR was increased in GATA-2 overexpressing K562 cells. These findings suggest that GATA-2 could induce erythroid-specific genes without competition with GATA-1 when expressed in erythroid-committed cells, and thus further suggest that temporal and spatial regulation may be important for displaying specific functions of GATA-2.
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PMID:Induction of erythroid-specific genes by overexpression of GATA-2 in K562 cells. 1686