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)

We have identified and sequenced a cDNA encoding human neutrophil collagenase from a lambda gt11 cDNA library constructed from mRNA extracted from the peripheral leukocytes of a patient with chronic granulocytic leukemia. The library was screened with an oligonucleotide probe constructed from the putative zinc-binding region of fibroblast collagenase. Eleven positive clones were identified, of which the one bearing the largest insert (2.2 kilobases (kb)) was sequenced. From the nucleotide sequence of the 2.2-kb cDNA clone we have deduced a 467-amino acid sequence representing the entire coding sequence of the enzyme. The deduced protein was confirmed as neutrophil collagenase by conformity with the amino-terminal sequence analyses of three tryptic peptides of purified neutrophil collagenase. The cDNA clone hybridizes to a 3.3-kb mRNA present in RNA extracted from human bone marrow but did not hybridize with RNA isolated from U937 cells induced to differentiate with phorbol myristate acetate. Neutrophil collagenase was found to possess 57% identity with the deduced protein sequence for fibroblast collagenase with 72% chemical similarity. Certain regions of the molecule, including the putative zinc-binding region, are highly conserved. When compared with the published sequence for fibroblast collagenase, neutrophil collagenase contains four additional sites for glycosylation. Medium from COS-7 cells transfected with a pcDNA1 eucaryotic expression vector containing cDNA for neutrophil collagenase degraded type I collagen into the three-quarter, one-quarter fragments characteristic of mammalian interstitial collagenase activity. Thus, definitive evidence based on the cDNA sequence confirms the neutrophil collagenase is a distinct gene product and a member of the family of matrix metalloproteinases.
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PMID:Human neutrophil collagenase. A distinct gene product with homology to other matrix metalloproteinases. 216 2

A novel erythroid cell line, RM10, was established from a long-term bone marrow culture of a patient with chronic myelogenous leukemia (CML). RM10 cells were positive for periodic acid Schiff (PAS), but negative for peroxidase and dual esterase. RM10 cells had la, pre B (CD10), myeloid (CD13, CD14, CD33) and erythroid (glycophorin A) markers, but had no other lymphoid, megakaryocytic, or mesenchymal cell markers. RM10 cells spontaneously synthesized hemoglobin, which was markedly enhanced with hemin. Isoelectric focusing of the cell lysates and northern blot analysis of the total cellular RNA revealed hemoglobin synthesis in the cells. Using 125I-labeled recombinant human erythropoietin (Epo), two classes of Epo receptors were demonstrated in the RM10 cells. However, Epo did affect neither growth nor erythroid differentiation of the cells. RM10 cells rapidly differentiated to monocytic cells in the presence of 12-0-tetradecanoylphorbol-13-acetate, and simultaneously expressed glycoprotein IIb/IIIa. RM10 cells had Philadelphia chromosome (Ph), and expressed p210bcr-abl using immunoprecipitation with anti-c-abl and anti-phosphotyrosine antibodies. These results indicate that the RM10 cells have the characteristics of multipotential hemopoietic cells originating from Ph-positive CML and that high affinity Epo receptor class is not a sufficient condition for Epo responsiveness.
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PMID:A novel CD10-positive erythroid cell line, RM10, established from a patient with chronic myelogenous leukemia. 216 10

We have analyzed morphological and biochemical changes occurring during megakaryocytic differentiation of the human chronic myelogenous leukemia cell line K562 induced by phorbol 12-myristate 13-acetate (PMA). PMA-treated cells became growth arrested, were slightly larger and irregular in shape, adhered better to the culture flask surface, and expressed the glycoprotein IIIa on their surfaces. The morphological changes induced by PMA treatment were associated with the disappearance of actin from the cytosol and presumably reflect PMA-induced actin polymerization. Megakaryocytic differentiation was accompanied by about a 3-fold decrease in the specific phosphotyrosine protein phosphatase (PTPase) activity in the particulate membrane fraction, whereas the activity in the soluble cytosol fraction increased about 3-fold. The decrease of PTPase activity in the particulate membrane fraction could be attributed to the disappearance of at least 1 distinct PTPase form displaying an apparent native Mr of 200,000 and a reduction in activity of a Mr 43,000 PTPase found associated with membranes of all cells examined to date. The increase of PTPase activity in the cytosol fraction manifested itself by the appearance of a new Mr 40,000 PTPase and a reduction of a Mr 60,000 PTPase. These results suggest the existence of several growth- and/or differentiation-related PTPase activities in K562 cells.
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PMID:Megakaryocytic differentiation of K562 cells is associated with changes in the cytoskeletal organization and the pattern of chromatographically distinct forms of phosphotyrosyl-specific protein phosphatases. 216 44

A 43-year-old woman with Ph1-positive chronic myelogenous leukemia (CML) was diagnosed as having blastic crisis. The phenotype of blasts was CD9+, CD10+, CD19+, CD11b+ and CD33+, suggesting the B Lymphoid and myeloid mixed lineage. Two color analysis of CD10 and CD33 revealed that 50% of blast cells had both B lymphocyte- and myelomonocyte-associated surface markers. Rearrangement of the immunoglobulin heavy chain gene was detected. After culturing blasts with 12-o-tetradecanoyl-phorbol 13 acetate (TPA), basophilic granules appeared in cytoplasm of the cells. These granules were positive for toluidine blue staining. This finding that the biphenotypic blasts expressing both B lymphoid and myelomonocytoid features differentiated into basophils suggests that blasts of this case are derived from a common progenitor of B lymphoid and myeloid lineages including basophil.
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PMID:[Blast crisis of chronic myelogenous leukemia with blasts expressing both immature B lymphocyte- and myelomonocyte-associated antigens and differentiating into basophils in vitro]. 221 82

The effects of TPA (12-0-tetradecanoylphorbol-13-acetate) and RA (retinoic acid) were investigated on the cell lines HL60 (acute promyelocytic leukemia) and K562 (erythroleukemia) and on cells from patients with several kinds of leukemia. There were 14 cases of acute lymphocytic leukemia (ALL), 2 cases of chronic lymphocytic leukemia (CLL), 23 cases of acute myeloid leukemia (M1-M7), 5 cases of chronic myelocytic leukemia in blast crisis (CML-BC) and 2 mixed leukemias. In almost all of the cases examined, after TPA exposure cells from patients with proven myeloid leukemia became adherent to the substrate, while lymphoid leukemia cells remained in suspension, allowing the differentiation of lymphoid from myeloid blasts. The only exception was in one case of CLL, which had cells that became adherent with long filamental projections. In addition, increased phagocytosis following TPA exposure permitted characterization of M7 as this was the only myeloid leukemia negative for phagocytosis. Further discrimination between the subtypes of myeloid leukemia could be based on the increased lysozyme production seen after TPA in M4 and M5. Esterase positivity allowed the discrimination of M1 cells, which were negative before and after TPA treatment. In agreement with the results of other authors, TPA and RA led to independent ways of differentiation, granulocytic-like lineage and monocytic-like cells being favored by RA and TPA, respectively. The capacity of the same cell to differentiate into more than one lineage, depending on whether RA or TPA was used, was only seen in the present study with M3 cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myeloid leukemia differentiation by phorbol ester and retinoic acid: a practical approach. 223 Nov 80

We present, to our knowledge, the first extensively studied case of lymphoid L2 blast crisis of chronic myelogenous leukemia with a hand mirror cell (HMC) variant. Special stains revealed the leukemic cells to be terminal deoxynucleotidyl transferase positive by immunofluorescence and cytochemically positive for alpha-naphthyl acetate esterase and acid phosphatase (diffuse granular). Immunophenotyping identified the major leukemic cell population as B-cells that expressed CD10+, CD19+, and HLA-DR+. It was not possible to separate the HMC and the non-HMC leukemic population by gating various cell populations, dual staining, cytochemistry, or by terminal deoxynucleotidyl transferase. Gene rearrangements were observed in both Ig heavy-chain alleles and one T-cell antigen receptor gamma-subunit allele. The rearrangements occupied all of the cells, indicating that the HMC and non-HMC were of a common clonal origin. The patient had a mosaic karyotype, with 90% of the cells having t(9;22), t(8;14), and t(9;15) translocations, an additional chromosome 8, and deleted chromosomes 9 and 15. Antibodies to simian sarcoma-associated virus and baboon endogenous virus were isolated in the patient's peripheral blood plasma.
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PMID:Lymphoblastic crisis of chronic myelogenous leukemia. Hand mirror variant. 236 26

Tumor necrosis factor alpha (TNF-alpha) and gamma-interferon (IFN-gamma) have been shown to suppress clonogenic growth in cultures containing blast cells obtained from patients with acute myeloid leukemia. We report that recombinant human TNF-alpha and IFN-gamma are also able to induce functional and morphological maturation in fresh myeloid leukemic cells in vitro. Assessing suspension cultures containing cells from patients with acute myeloid leukemia (11 patients) or myeloid blast crisis of chronic myeloid leukemia (5 patients), it was found that recombinant human TNF-alpha and IFN-gamma significantly enhanced the number of cells reducing nitroblue tetrazolium, as compared to control cultures containing no cytokine (P less than 0.001 and P less than 0.001, respectively). Cells from responders showed alterations characteristic of monocyte/macrophage differentiation, adherence to plastic surfaces, development of positive staining for alpha-naphthyl acetate esterase, typical morphology, and expression of cell surface antigens detected by the monoclonal antibodies Mo-1, Mo-2, and My-4. Both cytokines decreased the number of viable cells, the number of blast cells, and the number of cluster-forming units in suspension culture, suggesting inhibitory actions on the growth capacity of leukemic cells. Compared to the maximum effects of either factor alone, the combination of recombinant human TNF-alpha and IFN-gamma significantly increased the extent of growth inhibition and cell adherence but did not result in further increases in nitroblue tetrazolium reduction. The presence of Auer rods in IFN-gamma or TNF-alpha differentiation-induced macrophages with cells from a patient with M5 acute myeloid leukemia demonstrates that these cytokines can induce differentiation of a leukemic clone in primary cells from patients with leukemia.
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PMID:Differentiation-inducing effect of recombinant human tumor necrosis factor alpha and gamma-interferon in vitro on blast cells from patients with acute myeloid leukemia and myeloid blast crisis of chronic myeloid leukemia. 249 71

The human chronic myeloid leukemia cell line K562 acquires several megakaryoblastoid features when cultured in the presence of the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). We observed strongly increased secretion of several proteins into the culture media of K562 cells within a few hours of TPA treatment. Two of the major secreted polypeptides were identified by immunoprecipitation from media of metabolically labeled cultures as the tissue inhibitor of metalloproteinases (TIMP) and the type 1 plasminogen activator inhibitor (PAI-1). Maximal amounts of PAI-1 mRNA and secretion of PAI-1 polypeptides were observed after 24 hr of TPA treatment and PAI-1 persisted at elevated levels for several days. The induction of PAI-1 mRNA was dependent on de novo protein synthesis. Uninduced and induced cells secreted urokinase plasminogen activator in its single-chain proenzyme form (pro-u-PA), which was cleaved extracellularly to the active two-chain form as shown by pulse-chase labeling experiments. Upon TPA induction, the secretion of u-PA polypeptides increased severalfold, and there was a transient accumulation of pro-u-PA in the culture medium. However, this did not lead to increased u-PA activity in the cultures, since active u-PA was removed by complex formation with the large excess of coinduced PAI-1. Induction of u-PA mRNA was biphasic: The first peak of about tenfold increase in steady-state u-PA mRNA at 3 hr was followed by a steep decline to the baseline level at 12 hr, and a second, slower accumulation of u-PA mRNA occurred over the next few days. The biphasic accumulation of u-PA mRNA was also reflected in u-PA protein synthesis. We conclude that concerted changes in favor of a nonproteolytic extracellular environment occur in TPA-induced K562 cultures undergoing megakaryoblastoid differentiation. These changes include excessive secretion of TIMP and inhibition of the induced u-PA by the simultaneous accumulation of PAI-1.
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PMID:Down-regulation of proteolytic activity in 12-O-tetradecanoyl-phorbol-13-acetate-induced K562 leukemia cell cultures: depletion of active urokinase by excess type 1 plasminogen activator inhibitor. 250 Apr 50

The c-fms protooncogene encodes the receptor for the colony-stimulating factor 1 of macrophages. Its transforming counterpart, the v-fms oncogene has previously been recognized as the transforming gene of the McDonough strain of feline sarcoma virus. We have isolated rabbit antisera against a 115-kDa recombinant polypeptide containing the 926 carboxy-terminal amino acids of the v-fms protein. All antibodies recognized the cytoplasmic domain of the v-fms protein, which is 95% homologous to the corresponding domain of human c-fms proteins. These sera were applied in a survey of various human cancer cell lines, such as peripheral blood mononuclear (HL60) and choriocarcinoma (BeWo) cells, as well as leukemic cells from 58 patients with acute myelocytic, chronic myelocytic or acute lymphocytic leukemias (AML, CML, ALL). Significantly enhanced levels of fms-specific tyrosine kinase activity were detected in 12-O-tetradecanoylphorbol-13-acetate-induced HL60 and in BeWo cells, and in 7 out of 24 samples from AML patients, whereas no activity could be detected in 9 ALL or in 25 CML cell preparations. The AML cells were classified according to the FAB criteria. The highest incidence of increased fms activity was found in cells assigned to the M4 class (four out of five cases). While no activity was found in material belonging to FAB classes M2 or M3, one of the two cases of the M5 class was kinase-positive. Interestingly, two out of seven cases of the M1 class cells exhibited enhanced levels of fms kinase. These data suggest that the determination of the fms kinase may be useful to subdivide the M1 class of the FAB classification into monocytic and non-monocytic precursor leukemia cells.
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PMID:Detection of fms-oncogene-specific tyrosine kinase activity in human leukemia cells. 252 17

Adherence reactions involving human leukocytes are mediated by a family of glycoprotein surface antigens composed of three different alpha subunits designated alpha L, alpha M, and alpha X, each of which is associated with a single beta subunit in an alpha 1 beta 1 heterodimer structure. We cloned the cDNA for the common beta subunit and investigated beta subunit mRNA expression in HL-60 promyelocytic leukemia cells and human granulocytic cells. Leukocyte adherence receptor beta subunit mRNA transcripts were present in low levels in HL-60 myeloblasts and promyelocytes and increased 10-fold or greater with chemically induced differentiation to more mature granulocytes (using retinoic acid and dimethylformamide) or monocyte/macrophages (using phorbol myristate acetate). Levels of beta subunit mRNA expression were also increased both in normal human peripheral blood granulocytes and in granulocytes from patients with chronic myelogenous leukemia. Nuclear run-off assays indicated that the increased steady state level of the beta subunit mRNA in retinoic acid-differentiated HL-60 cells was secondary to enhanced beta subunit gene transcription. We conclude that mRNA levels for the beta subunit of the receptor on human leukocytes that mediates cellular adherence are increased in more mature granulocytic cells compared to immature myeloid precursors and that this enhanced mRNA expression is transcriptionally regulated.
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PMID:Transcriptional regulation of the leukocyte adherence protein beta subunit during human myeloid cell differentiation. 290 19


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