Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutrophils synthesize and store intracellularly a 92-kDa type IV collagenase (gelatinase), the primary structure of which is unknown. We designed a primer based on the highly conserved cysteine-switch region of metalloproteinases and employed the polymerase chain reaction to generate a probe of the human neutrophil gelatinase (HNG) gene. This probe was used to clone the cDNA encoding HNG by screening a chronic granulocytic leukemia cDNA library. In vitro translation of the cDNA-derived HNG mRNA yielded a major product of 78 kDa and smaller autolytically activated or degraded products, all of which were recognized by anti-HNG antibody. The HNG cDNA sequence is nearly identical to that encoding a 92-kDa gelatinase secreted by HT1080 cells. In addition, primer extension and S1 analysis reveal that the above two gelatinase transcripts have similar initiation sites. The HNG cDNA hybridized to a 2.8-kilobase mRNA from chronic granulocytic leukemia cells. HNG mRNA expression was absent from uninduced HL60 cells and from HL60 cells induced to granulocytic maturation with Me2SO. However, unlike other neutrophil secondary granule genes, HNG mRNA was detected in HL60 cells induced to monocytic maturation with 12-O-tetradecanoylphorbol 13-acetate. This suggests that the HNG gene may be subject to differential control pathways in two related but distinct hematopoietic lineages.
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PMID:Structure and expression of neutrophil gelatinase cDNA. Identity with type IV collagenase from HT1080 cells. 146 22

The two matrix metalloproteinases (MMPs) Mr 72,000 type IV collagenase (MMP-2, gelatinase A) and Mr 92,000 type IV collagenase (MMP-9, gelatinase B) play key roles in tissue remodeling and tumor invasion by digestion of extracellular matrix barriers. We have investigated the production of these two enzymes as well as the membrane-type MMP (MT1-MMP) and the tissue inhibitors of metalloproteinases (TIMPs) TIMP-1 and TIMP-2 in the bone marrow mononuclear cells (BM-MNCs) of patients with acute myeloid leukemia (AML; n = 24), chronic myeloid leukemia (CML; n = 17), myelodysplastic syndromes (MDS; n = 8), and healthy donors (n = 5). Zymographic analysis of BM-MNC-conditioned medium showed that a Mr 92,000 gelatinolytic activity, identified as MMP-9 by Western blotting, was constitutively released from cells of all patients and healthy individuals examined in this study. In contrast, MMP-2 secretion was found to be absent in all samples from healthy donors but present in 8 of 11 (73%) of the samples from patients with primary AML, 7 of 8 (88%) with secondary AML, and only 1 of 5 (20%) cases with AML in remission, indicating MMP-2 to be produced by the leukemic blasts. MMP-2 release was not detected in CML cell-conditioned medium with the exception of two cases, both patients either being in or preceding blast crisis. In MDS, MMP-2 was found in three of eight (38%) of the patients, two of them undergoing progression of disease within 12 months. Quantitative Northern blot analysis in freshly isolated BM-MNCs showed a relatively low constitutive expression of TIMP-1 in all samples, whereas MMP-9 gene transcription was higher in healthy donors and CML samples, than in AML and MDS. Reverse transcriptase-PCR analysis revealed the presence of TIMP-2 mRNA in the majority of MMP-2-releasing BM-MNCs. MT1-MMP expression was present in most samples of patients with MDS or AML but absent in those with secondary AML and CML. Thus, we have shown that BM-MNCs continuously produce MMP-9 and TIMP-1 and demonstrated that leukemic blast cells additionally secrete MMP-2 representing a potential marker for dissemination in myeloproliferative malignancies.
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PMID:Matrix metalloproteinase production by bone marrow mononuclear cells from normal individuals and patients with acute and chronic myeloid leukemia or myelodysplastic syndromes. 1035 46

To characterize molecular mechanisms operating in chronic myeloid leukemia (CML) cells with a view toward development of novel therapeutic targets, we analyzed gene-expression profiles of cancer cells from 27 CML patients using a cDNA microarray representing 23,040 human genes. By comparing expression patterns of CML with those of normal cells, we identified 150 genes that were commonly highly up-regulated in CML cells. In addition to 54 genes (34 of them ESTs) whose functions are currently unknown, the up-regulated elements included genes encoding cell-cycle regulators, transcriptional activators, transcriptional factors, and protein kinases as well as proteins already known to be induced in CML, such as some hemoglobins, haptoglobin (HP1), and matrix metalloproteinase 9 (MMP-9), a protein involved in tissue remodeling and tumor invasion. On the other hand, our protocol selected 106 genes, including 13 of unknown function, as being commonly significantly down-regulated in all phases of CML. The results of semiquantitative RT-PCR experiments with 11 representatives of the up-regulated group supported the reliability of our microarray analysis. These data should provide useful information for finding candidate genes whose products might serve as molecular targets for treatment of CML patients.
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PMID:Genome-wide analysis of gene-expression profiles in chronic myeloid leukemia cells using a cDNA microarray. 1288 4