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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the significance of GATA-2 and immunoglobulin heavy chain germline gene C( micro ) (IgH germline gene C( micro )) expression and coexpression in various leukemia cells, GATA-2 and IgH germline gene C( micro ) mRNA in bone marrow and peripheral blood cells from 63 leukemia patients were detected by reverse transcription-polymerase chain reaction (RT-PCR). No GATA-2 or IgH germline gene C( micro ) mRNA were detected in normal bone marrow and peripheral blood. GATA-2 mRNA were be detected in 91.3% patients with acute myeloid leukemia (AML), 75% patients with acute lymphoblastic leukemia (ALL) as well as 83.3% patients with chronic myeloid leukemia (CML-CP); IgH germline gene C( micro ) mRNA were be identified in 47.8% AML, 41.6% ALL, as well as 5.6% CML-CP. All patients with CML-AP and CML-BC expressed GATA-2 mRNA and partly expressed IgH germline gene C( micro ) mRNA. 47.8% AML and 41.6% ALL patients coexpressed GATA-2 and IgH germline gene C( micro ) mRNA. GATA-2(+) IgH germline gene C( micro )(+) cells of AML and ALL were mainly HLA-DR positive. As aberration of the transcription factors, GATA-2 and germline IgH germline gene C( micro ) gene might been linked to leukemogenesis. Various expression of GATA-2 and germline IgH germline gene C( micro ) gene in leukemia might correlated with the heterogeneous differentiation level of leukemia cells. The fact that leukemia with GATA-2(+) IgH germline gene C( micro )(+) coexpression indicated multilineage impairment of hematopoietic cells.
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PMID:[Expression of GATA-2 Gene and Immunoglobulin Heavy Chain Germline Gene C( micro ) in Leukemia Cells and Its Significance] 1257 77

Transcription factor GATA-2 is a member of GATA family which binds a common DNA sequence motif [T/A (GATA) A/G] through an evolutionarily conserved zinc finger domain. An essential role for GATA-2 in the development of hematopoietic cells has recently been shown in gene knockout experiments in mice. GATA-2 gene disruption makes reduction in all hematopoietic precursors, whereas enforced expression of GATA-2 blocks normal hematopoiesis. GATA-2 exerts regulation in early embryo and cooperates with other GATA transcription factors in proliferation and differentiation of myeloid, erythroid, megakaryocytic and mast cell lineages. GATA-2 mRNA and protein could be detected in human myelogenous leukemia cell lines and in most patients with primary leukemias. Some data revealed that GATA-2 could transactivate the Cas-Br-E and graffi retroviruses, which can induce myelogenous leukemia in mice. However, the role of GATA-2 in pathogenesis of leukemia is still not well understood.
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PMID:The Role of Transcription Factor GATA-2 in Early Hematopoiesis. 1257 22

Hex is one of the homeobox genes suggested to be important for hematopoietic cell differentiation. However, its biological function and mechanism of transcriptional regulation in hematopoietic cells remain elusive. We have identified the regulatory region necessary for transcription of the mouse Hex gene in K562 leukemia cells through transient reporter assays involving various deletion mutants. This region, comprising +775 to +1177 in the first intron, had enhancer-like properties and showed high activity in other hematopoietic cell lines such as U937, HEL, and RAW264.7, but little activity in other Hex-expressing cell lines such as MH(1)C(1) and H4IIE hepatoma cells, suggesting that this region functions as a hematopoietic cell-specific enhancer-like element. Binding site mutation of hematopoietic transcription factors, such as GATAs and c-Myb present in the enhancer-like element, significantly decreased the luciferase reporter gene expression in K562 cells. Electrophoretic mobility shift assays showed that GATA-1, GATA-2, or c-Myb actually binds to three of these putative binding sites, and also suggested that several unidentified factors might interact with the enhancer-like element. Overexpression of GATA-1, GATA-2, or c-Myb stimulated the enhancer-like activity via these three binding sites. Thus, we conclude that Hex expression in hematopoietic cells is mainly regulated by GATA-1, GATA-2, and c-Myb via this intronic enhancer-like element.
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PMID:Identification and characterization of the hematopoietic cell-specific enhancer-like element of the mouse hex gene. 1504 29

The hierarchical gene regulatory network in hematopoiesis is highly complex, making elucidation of the processes of specification and differentiation of hematopoietic cells a challenging task. Recent discoveries have divulged the GATA factors as central to the genetic control of hematopoiesis. In particular, hematopoietic development is subject to extensive and precise regulation of GATA-1 and GATA-2 at the molecular level. We wish to emphasize the regulatory relationships between GATA-1 and GATA-2 implicated in cell development. An advanced experimental genetic approach has provided evidence that abnormalities in this network may result in a variety of blood disorders. The most striking new finding is the novel pathogenesis arising from GATA-1 dysfunction that leads to leukemia.
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PMID:Gene expression regulation and domain function of hematopoietic GATA factors. 1565 47

Glycoprotein VI (GPVI) is an essential platelet receptor for collagens that is exclusively expressed in the megakaryocytic lineage. Transcription of the human gene GP6 is driven largely by GATA-binding protein 1 (GATA-1), specificity protein 1 (Sp1), and Friend leukemia integration 1 (Fli-1). In this report, we show that GPVI expression during megakaryocytic differentiation is dependent on cytosine-phosphate-guanosine (CpG) demethylation that can be initiated by thrombopoietin (TPO). Sodium bisulfite genomic sequencing established that a CpG-rich island within the GP6 promoter region is fully methylated at 10 CpG sites in GPVI-nonexpressive cell lines, such as UT-7/EPO and C8161, but completely unmethylated in GPVI-expressive cell lines, including UT-7/TPO and CHRF288-11. To further confirm the relationship between CpG demethylation and expression of GPVI in primary cells, we treated human cord blood cells with TPO. The GP6 promoter is highly methylated in cord blood mononuclear cells (progenitors) but not in CD41+-enriched cells obtained after TPO differentiation. Furthermore, when UT-7/EPO-Mpl cells, which stably express human C-myeloproliferative leukemia virus ligand (c-Mpl), were treated with TPO, demethylation of the GP6 promoter was induced. In every case, demethylation of the GP6 promoter correlated with an increase in mRNA level. Thus, megakaryocyte-specific expression of the GP6 gene is regulated, in part, by CpG demethylation, which can be directly initiated by TPO.
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PMID:Thrombopoietin initiates demethylation-based transcription of GP6 during megakaryocyte differentiation. 1570 20

In order to investigate expressions of transcription factor GATA-1 and GATA-2 genes in the bone marrow stromal cells (BMSCs) from patients with leukemia or normal controls, bone marrow stromal cells from 34 normal cases and 42 cases with leukemia were cultured long-term in vitro. Nonadherent cells (bone marrow hematopoietic cells) and amplified adherent cells (BMSC) were collected separately. Expressions of GATA-1 and GATA-2 genes were analyzed by using RT-PCR-ELISA; the semi-quantitative expression levels of GATA genes in the BMSCs from patients with leukemia were compared with normal controls. The results showed that expressions of GATA-1 and GATA-2 genes could be detected in the BMSCs and the bone marrow hematopoietic cells from both normal controls and the cases of leukemia. The expression ratio of GATA-1 in the BMSCs from acute lymphocytic leukemia (ALL) (85.7%) was similar to the normal controls (88.2%), whereas the expression ratios in BMSCs from acute myelocytic leukemia (AML) (55.6%) and chronic myelocytic leukemia (CML) (41.2%) were significant lower than the normal controls (P < 0.05). The rank of expression level of GATA-1 gene in the BMSCs was "ALL>AML>normal>CML". There was no difference in the expression level of GATA-2 gene within the BMSCs from normal controls and patients with leukemia. The ranks of expression levels of GATA-1 and GATA-2 genes in bone marrow hematopoietic cells were "AML>normal>ALL>CML" and "AML>CML>ALL>normal". The dominant expression of GATA-2 gene was found in the BMSCs from AML, CML or normal controls. It is inferred that the expressions of GATA-1 and GATA-2 genes in the BMSCs of normal controls and patients with leukemia may influence the regulation of hematopoiesis in the bone marrow stroma and it is worthy of further study to explore their roles in pathogenesis and development of leukemia.
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PMID:[Expressions of transcription factor GATA-1 and GATA-2 genes in bone marrow stromal cells from patients with leukemia]. 1574 39

A number of transcription factors (TFs) have been reported that play crucial roles in hematopoiesis. However, only little is known about how these factors are involved in the mechanisms of hematopoietic development and lineage commitment. To investigate the roles of TFs in human B-cell precursors (BCPs), the present study analyzed the expression of the following 16 hematopoietic TFs: AML1, C/EBPalpha, C/EBPbeta, C/EBPgamma, C/EBPepsilon, E2A, Ets-1, GATA-1, GATA-2, GATA-3, Ikaros, IRF-1, Pax5, PU.1, T-bet and TCF-1 in 30 human BCP-leukemia cell lines. All BCP-leukemia cell lines were found to be positive for the expression of AML1, C/EBPgamma, E2A, Ets-1, IRF-1, Pax5 and PU.1 at the mRNA level. The mRNA expression of C/EBPalpha, C/EBPbeta, C/EBPepsilon, GATA-2, Ikaros, T-bet and TCF-1 was detected in 2 to 29 of the cell lines. Eight BCP-cell lines showed positivity for the dominant negative Ikaros isoform Ik6, while others were positive for expression of Ik1, 2, 3 and 4. GATA-1 and GATA-3 were universally negative. The expression of C/EBPalpha, PU.1 and T-bet was positive at the protein level in five, 29 and four out of 30 BCP-cell lines, respectively. Cell lines were stimulated with interleukin (IL)-7 and/or interferon (IFN)-gamma to investigate the regulation of TF expression. T-bet was clearly induced in the two cell lines NALM-19 and NALM-29 after stimulation. C/EBPbeta and IRF-1 were up-regulated in both cell lines and TCF-1 was down-regulated in NALM-19. No significant changes were observed for the other 12 TFs. The present report could provide useful information in the study of the role of TFs on normal and malignant human BCPs.
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PMID:Transcription factor expression in B-cell precursor-leukemia cell lines: preferential expression of T-bet. 1592 79

Individuals with Down syndrome (DS) are predisposed to develop acute megakaryoblastic leukemia (AMKL), characterized by expression of truncated GATA1 transcription factor protein (GATA1s) due to somatic mutation. The treatment outcome for DS-AMKL is more favorable than for AMKL in non-DS patients. To gain insight into gene expression differences in AMKL, we compared 24 DS and 39 non-DS AMKL samples. We found that non-DS-AMKL samples cluster in two groups, characterized by differences in expression of HOX/TALE family members. Both of these groups are distinct from DS-AMKL, independent of chromosome 21 gene expression. To explore alterations of the GATA1 transcriptome, we used cross-species comparison with genes regulated by GATA1 expression in murine erythroid precursors. Genes repressed after GATA1 induction in the murine system, most notably GATA-2, MYC, and KIT, show increased expression in DS-AMKL, suggesting that GATA1s fail to repress this class of genes. Only a subset of genes that are up-regulated upon GATA1 induction in the murine system show increased expression in DS-AMKL, including GATA1 and BACH1, a probable negative regulator of megakaryocytic differentiation located on chromosome 21. Surprisingly, expression of the chromosome 21 gene RUNX1, a known regulator of megakaryopoiesis, was not elevated in DS-AMKL. Our results identify relevant signatures for distinct AMKL entities and provide insight into gene expression changes associated with these related leukemias.
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PMID:Identification of distinct molecular phenotypes in acute megakaryoblastic leukemia by gene expression profiling. 1649 68

Although leukemogenic tyrosine kinases (LTKs) activate a common set of downstream molecules, the phenotypes of leukemia caused by LTKs are rather distinct. Here we report the molecular mechanism underlying the development of hypereosinophilic syndrome/chronic eosinophilic leukemia by FIP1L1-PDGFRalpha. When introduced into c-Kit(high)Sca-1(+)Lineage(-) cells, FIP1L1-PDGFRalpha conferred cytokine-independent growth on these cells and enhanced their self-renewal, whereas it did not immortalize common myeloid progenitors in in vitro replating assays and transplantation assays. Importantly, FIP1L1-PDGFRalpha but not TEL-PDGFRbeta enhanced the development of Gr-1(+)IL-5Ralpha(+) eosinophil progenitors from c-Kit(high)Sca-1(+)Lineage(-) cells. FIP1L1-PDGFRalpha also promoted eosinophil development from common myeloid progenitors. Furthermore, when expressed in megakaryocyte/erythrocyte progenitors and common lymphoid progenitors, FIP1L1-PDGFRalpha not only inhibited differentiation toward erythroid cells, megakaryocytes, and B-lymphocytes but aberrantly developed eosinophil progenitors from megakaryocyte/erythrocyte progenitors and common lymphoid progenitors. As for the mechanism of FIP1L1-PDGFRalpha-induced eosinophil development, FIP1L1-PDGFRalpha was found to more intensely activate MEK1/2 and p38(MAPK) than TEL-PDGFRbeta. In addition, a MEK1/2 inhibitor and a p38(MAPK) inhibitor suppressed FIP1L1-PDGFRalpha-promoted eosinophil development. Also, reverse transcription-PCR analysis revealed that FIP1L1-PDGFRalpha augmented the expression of C/EBPalpha, GATA-1, and GATA-2, whereas it hardly affected PU.1 expression. In addition, short hairpin RNAs against C/EBPalpha and GATA-2 and GATA-3KRR, which can act as a dominant-negative form over all GATA members, inhibited FIP1L1-PDGFRalpha-induced eosinophil development. Furthermore, FIP1L1-PDGFRalpha and its downstream Ras inhibited PU.1 activity in luciferase assays. Together, these results indicate that FIP1L1-PDGFRalpha enhances eosinophil development by modifying the expression and activity of lineage-specific transcription factors through Ras/MEK and p38(MAPK) cascades.
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PMID:FIP1L1-PDGFRalpha imposes eosinophil lineage commitment on hematopoietic stem/progenitor cells. 1914 1

Although oncogenic functions and the clinical significance of Wilms tumor 1 (WT1) have been extensively studied in acute leukemia, the regulatory mechanism of its transcription still remains to be determined. We found a significant correlation among the amounts of WT1, GATA-1 and GATA-2 mRNAs from leukemia and solid tumor cell lines. Overexpression and small interfering RNA (siRNA) transfection experiments of GATA-1 and GATA-2 showed that these GATA transcription factors could induce WT1 expression. Promoter analysis showed that the 5' promoter did not explain the different WT1 mRNA levels between cell lines. The 3' enhancer, especially the distal sites out of six putative GATA binding sites located within the region, but not the intron 3 enhancer, were essential for the WT1 mRNA level. Electrophoretic mobility shift assay (EMSA) showed both GATA-1 and GATA-2 bound to these GATA sites. Besides acute leukemia cell lines, solid tumor cell lines including, TYK-nu-cPr also showed a high level of WT1 mRNA. We showed that GATA-2 expression is a determinant of WT1 mRNA expression in both TYK-nu-cPr cells and HL60 cells without GATA-1 expression. Taken together, these results suggest that GATA-1 and/or GATA-2 binding to a GATA site of the 3' enhancer of WT1 played an important role in WT1 gene expression.
Leukemia 2009 Jul
PMID:GATA-1 and GATA-2 binding to 3' enhancer of WT1 gene is essential for its transcription in acute leukemia and solid tumor cell lines. 1921 33


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