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)

A zinc-finger gene encoding a transcription factor that regulates hematopoiesis, MZF-1, is located at the extreme end of the q arm of human chromosome 19. Several lines of evidence indicate that MZF-1 lies less than 20 kb from the subtelomeric repeat region of 19q. Telomeres are known to degenerate as cells age; disruption of MZF-1 due to telomeric degeneration may play a role in the increased incidence of leukemia in the elderly.
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PMID:The location of MZF-1 at the telomere of human chromosome 19q makes it vulnerable to degeneration in aging cells. 863 24

The myeloid zinc finger protein MZF-1 is important in hematopoiesis. Previous studies have found that reducing expression of MZF-1 inhibited G-CSF-driven human marrow colony formation assays. In this study we found that retrovirally overexpressing MZF-1 in IL-3-dependent FDCP.1 cells inhibited their apoptosis when IL-3 was withdrawn. The MZF-1-transduced FDCP.1 cells also formed tumors when injected into congenic mice, whereas control FDCP.1 cells did not.
Leukemia 1996 Jun
PMID:Forced over-expression of the myeloid zinc finger gene MZF-1 inhibits apoptosis and promotes oncogenesis in interleukin-3-dependent FDCP.1 cells. 866 41

The expression of the human myeloid zinc finger gene (MZF-1) by human bone marrow cells is necessary for granulopoiesis. We have analyzed the structure and function of the MZF-1 gene by diagnostic polymerase chain reaction, genomic cloning, and promoter analysis. Comparison of human promyelocytic HL-60 cell cDNA with isolated MZF-1 genomic clones indicated that the human MZF-1 gene is without introns and spans approximately 3 kb. Restriction enzyme mapping and Southern analysis indicated further that the human MZF-1 gene is a single-copy gene. Primer extension studies identified the major transcription start site as a thymidine residue located 1102 bp upstream of the ATG translation start codon. A putative TATA box sequence (TAAAAA) was found at -66 bp and a CCAAT box at -130 bp relative to the transcription initiation site. In HL-60 cells, MZF-1 mRNA levels are increased by granulopoietic inducers including retinoic acid and GM-CSF. DNA upstream of the transcription start site contains tandem-repeated consensus retinoic acid response elements at -666 through -696 bp and paired putative GM-CSF-responsive sequences centered at -50 and -100 bp. CAT reporter gene constructs containing these DNA regions promoted transcription and conferred transcriptional responsiveness to retinoic acid and GM-CSF when transfected into HL-60 cells. Additional putative regulatory binding sites included conserved MZF-1 zinc finger binding sequences, the importance of which was suggested by the enhanced expression of the endogenous MZF-1 gene following vector-driven expression of MZF-1 constructs in K562 myeloblastic leukemia cells. These findings provide a clearer basis for understanding the role of MZF-1 gene expression in myeloid cell growth and differentiation.
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PMID:Isolation and functional characterization of the human gene encoding the myeloid zinc finger protein MZF-1. 884 78

The myeloid zinc finger gene, MZF-1, is a hematopoietic transcription factor expressed in developing myeloid cells. To characterize further the role of MZF-1 in myelopoiesis, we used retroviral gene transduction to overexpress MZF-1 in HL-60 cells to produce HL-60-MZF-1 cells. HL-60 cells respond to retinoic acid (RA) with growth inhibition, granulocytic differentiation and apoptosis. However, HL-60-MZF-1 cells exposed to RA continue to proliferate in response to RA as evidenced by a higher percentage of cells in S phase, higher peak cell counts, and later peak cell counts. Morphologic differentiation of the RA-induced HL-60-MZF-1 cells is delayed with half as many of the HL-60-MZF-1 cells compared to the wild-type HL-60 cells that are differentiated after 3 days of RA, although both cells types responded with 80-95% mature granulocytes after 6 days of RA. Apoptosis was delayed in the MZF-1 transduced cells as measured by internucleosomal DNA fragmentation patterns, the terminal transferase end labeling reaction (TUNEL), and quantitation of fragmented DNA by the diphenylamine reaction. Several markers of differentiation were identical in both HL-60 and HL-60-MZF-1 cells including CD11b, CD33, CD34, CD13, CD16 and CD14. However, following 6 days of RA, only half as many HL-60-MZF-1 cells expressed CD18 compared to the wild-type HL-60 cells. Expression of the bcl-2 proto-oncogene transcript and protein was higher in the HL-60-MZF-1 cells compared to wild-type HL-60s and expression persisted for 5 days following RA in the HL-60-MZF-1 cells compared to only 3 days in the parental HL-60 cells suggesting that bcl-2 may contribute to the inhibition of apoptosis. Overexpression of MZF-1 had no effect on PMA-induced monocyte/macrophage differentiation of HL-60 cells. Together these findings indicate that MZF-1 can stimulate cell proliferation and delay RA-induced differentiation and apoptosis in HL-60 cells. MZF-1 may function in a similar role in myelopoiesis allowing myeloid precursors to expand their numbers before going on to terminally differentiate.
Leukemia 1998 May
PMID:The myeloid zinc finger gene (MZF-1) delays retinoic acid-induced apoptosis and differentiation in myeloid leukemia cells. 959 66

A new human leukemia cell line with an eosinophilic phenotype, designated YJ, was established from the peripheral blood cells of a patient with chronic myelomonocytic leukemia (CMMoL) with eosinophilia. When cultured in RPMI 1640 medium containing 10% fetal bovine serum, most YJ cells were myeloblastoid with a small number of the cells having eosinophilic granules. Cell surface markers in the YJ cells were positive for CD33 and were negative for CD34, CD16 and CD23. The eosinophilic characteristics of YJ cells were confirmed by histochemical staining with Fast-Green/Neutral-Red and by the expression of mRNAs for eosinophil-associated granule proteins, eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN), eosinophil peroxidase (EPO), and major basic protein (MBP), and for the Charcot-Leyden crystal (CLC) protein. The YJ cells could be induced towards monocytic differentiation by stimulation with phorbol 12-myristate 13-acetate (PMA). The monocytic characteristics of YJ cells treated with PMA were confirmed by morphological analysis with alpha-naphthyl butyrate esterase staining, by CD14 expression, and by increased expression of Egr-1 mRNA. Furthermore, YJ cells could be differentiated towards the neutrophil lineage by stimulation with all-trans retinoic acid (RA). YJ cells treated in vitro with 2 microM RA differentiated into metamyelocytes and band neutrophils, and increased the number of nitroblue tetrazolium (NBT)-positive cells and increased gp91phox mRNA expression. Thus, the YJ cell line exhibited eosinophilic characteristics, but was able to differentiate to the monocytic or neutrophilic lineages in response to PMA or RA, respectively. The expression of genes for transcription factors involved in myeloid differentiation was evaluated by Northern blot analysis. Increased expression of Egr-1 was observed with macrophage differentiation. In contrast, increased expressions of C/EBPbeta and MZF-1 mRNA occurred with neutrophilic differentiation. The YJ cell line should be useful for elucidating the molecular mechanisms governing lineage switching from the eosinophil to monocytic or neutrophil lineages.
Leukemia 1998 Sep
PMID:Models of lineage switching in hematopoietic development: a new myeloid-committed eosinophil cell line (YJ) demonstrates trilineage potential. 973 93

Approximately 20% of adult patients with acute myeloid leukemia fail to achieve remission with initial induction chemotherapy, and around half ultimately experience relapse after achieving complete remission. Relapse continues to be a major hurdle in achieving cure after obtaining remission with induction chemotherapy in patients with acute myeloid leukemia. In last two decades, the immunogenic vaccine, involving peptide, protein, or DNA, has brought new perspectives for tumor immunotherapy. MLAA-34 is a newly identified monocytic leukemia-associated antigen. Downregulation of MLAA-34 expression significantly suppressed the proliferation of U937 cells in vitro and increased the spontaneous apoptosis of leukemia. However, the regulatory mechanisms of MLAA-34 gene are still unknown at present. Analysis of the promoter region of the MLAA-34 gene and reporter gene assays revealed that 600 bp core region was responsible for its regulation. In addition, our study indicated that E2F1 acts as a transcription repressor and MZF-1 acts as a transcription activator of the MLAA-34 gene.
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PMID:Regulation of expression of MLAA-34 gene through transcriptional factors E2F1 and MZF-1. 3193 32