Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The only ras oncogene as yet identified in cells from human fibrosarcomas is N-ras, but the relationship between N-ras oncogene expression and the malignant state of these cell lines is not known. To determine if expression of an N-ras oncogene causes human cells to become malignant, we transfected the N-ras oncogene from human leukemia cell line 8402, cloned into a high expression vector pSV N-ras, into MSU-1.1 cells, a nontumorigenic, infinite life span fibroblast cell strain with a normal morphology and a stable near-diploid karyotype. The transformants formed distinct foci composed of morphologically transformed cells. Cells from such foci expressed higher than normal levels of N-ras protein, exhibited growth factor independence, and formed large colonies in soft agar at a high frequency. Injection of progeny of these focus-derived cells s.c. into athymic mice resulted in progressively growing, invasive malignant tumors (round cell, spindle cell, or giant cell sarcomas) which reached a diameter of 6 mm in 3 to 4 weeks. Injection of focus-derived or tumor-derived cells i.v. resulted in tumors in various organs of the mice. The focus-derived cell strain tested, as well as the majority of the cells derived from the tumor it produced, exhibited the same near-diploid karyotype as the parental MSU-1.1 cells. Cells transfected with an N-ras oncogene that was expressed at a normal level formed only a single, indistinct focus, and cells from that focus were not malignant.
 ...
PMID:Malignant transformation of human fibroblasts by a transfected N-ras oncogene. 220 39

In an attempt to identify antigens expressed during breast differentiation, three murine monoclonal antibodies, CIBr2, CIBr7, and CIBr18, were produced against the human pleomorphic breast carcinoma cell line PMC42. All three monoclonal antibodies reacted with previously undescribed antigenic determinants on the PMC42 cell line. Antibody CIBr18 reacted only with the immunizing cell line PMC42, whereas antibodies CIBr2 and CIBr7 showed minimal reactivity toward a panel of 34 human leukemia- and solid tumor-derived cell lines. The antigenic determinants detected by the three antibodies were distinct, and each showed variable expression in PMC42 monolayer and organoid cultures. The heterogeneity of staining seen on PMC42 cultures may reflect the fact that this cell line contains up to eight morphologically distinct cell types. Antigen expression correlated with cell type in some instances, whereas in other instances phenotypic subdivision within a cell type was apparent. Antigens recognized by antibodies CIBr7 and CIBr18 were characterized biochemically. In Western blotting, antibody CIBr7 identified a single band of an apparent molecular weight of 38,000 within PMC42 cell lysates. Sodium dodecyl sulfate-polyacrylamide gel analysis of polypeptides immunoprecipitated by antibody CIBr18 from [35S]methionine-labeled PMC42 cell lysates identified two glycoproteins of apparent molecular weights of 115,000 and 120,000, respectively. No biochemical data for the CIBr2 antigen are yet available. All three antigens were detected in human mammary epithelium and some non-breast tissues. The expression of these antigens in normal and neoplastic mammary epithelia is discussed in terms of antigen heterogeneity and changes in antigen expression upon conversion to the malignant state.
 ...
PMID:Development of monoclonal antibodies to the human breast carcinoma cell line PMC42. 242 15

The colony-stimulating factors regulate growth, differentiation, and function of blood cells. The effect of granulocyte colony-stimulating factor (G-CSF) on myeloid leukemias is unique among colony-stimulating factors in driving the leukemic cells from a self-renewing malignant state to a mature differentiated phenotype with the concomitant loss of tumorigenicity. This property of G-CSF has led to suggestions that its absence is responsible for lack of differentiation of leukemic cells and that the therapeutic administration of G-CSF could reverse this defect and result in a cure for leukemia. Here we show that the gene coding for human G-CSF is localized to chromosome 17, bands q11.2-21. The translocation of the long arm of chromosome 17 at q12-21 to chromosome 15 is a specific abnormality occurring in a high proportion of, if not all, patients with acute promyelocytic leukemia, a disease characterized by undifferentiated myeloid cells and a dismal prognosis. Abnormalities of the regulation of a specific differentiation factor gene mediated by a specific chromosomal rearrangement may be directly implicated in the pathogenesis of human leukemia.
 ...
PMID:Localization of the human G-CSF gene to the region of a breakpoint in the translocation typical of acute promyelocytic leukemia. 244 21

As has been reported previously, head and neck carcinomas produce low molecular weight factors (H/N ca LMWFs); a molecular weight less than 25000 daltons is capable of inhibiting the chemotaxis of mononuclear phagocytes. The effect of the factors could be neutralized by antibodies to P15E, one of the structural envelope proteins of Murine Leukemia Viruses (MuLV). This indicates that these low molecular weight factors derived from the tumors are related to P15E. In this study, 35 biopsy specimens of head and neck carcinomas were subjected to an indirect immunoperoxidase assay, in order for P15E-like material to be detected morphologically. All head and neck carcinomas gave positive results. Sixty-three percent of other carcinomas (used as controls) were positive as well. P15E-like material was also expressed in epithelia-overlaying inflammatory responses. Healthy epithelia were not positive. This report thus supports the view that P15E-like molecules can be easily detected in cancerous disease--not only by way of biologic isolation, but also by use of immunohistochemical techniques. Since the factor is not specific for the malignant state, it cannot be used as a tumor marker. Possibly involved in the pathogenesis of cancerous disease, its relationship to growth factors, oncogenes, and the immune system needs further clarification.
 ...
PMID:Immunohistochemical detection of retroviral-P15E-related material in carcinomas of the head and neck. 310 7

In this article we present a patient with acute lymphoblastic leukemia (ALL) associated with eosinophilia, in which the eosinophilia preceded a meningeal and bone-marrow relapse of ALL. We analysed the purine and pyrimidine nucleotide content of the eosinophils (92% pure) and compared the nucleotide pattern with that of eosinophils from healthy donors and from patients with eosinophilia not associated with leukemia. The ratios of purine:pyrimidine and of uracil:cytosine nucleotides were decreased compared with those in eosinophils from healthy donors and from patients with eosinophilia with other aetiologies. The total nucleotide concentration was increased, especially the concentration of UDP-sugars and pyrimidine nucleotides. The decrease in these ratios and the increase in concentration of the nucleotides and the UDP-sugars were also detected in leukemic cells of patients with ALL (de Korte et al., Leukemia Res. 10, 389-396 (1986) compared to normal lymphocytes. We suggest a malignant character of the eosinophils in our patient with ALL associated with eosinophilia, in contrast with the non-malignant state suggested previously for these cells.
 ...
PMID:Abnormal nucleotide pattern in the eosinophils of a patient with acute lymphoblastic leukemia associated with eosinophilia. 346 43

Most drugs available for cancer chemotherapy exert their effects through cytodestruction. Although significant advances have been attained with these cytotoxic agents in several malignant diseases, response is often accompanied by significant morbidity and many common malignant tumours respond poorly to existing cytotoxic therapy. Development of chemotherapeutic agents with non-cytodestructive actions appears desirable. Considerable evidence exists which indicates that (a) the malignant state is not irreversible and represents a disease of altered maturation, and (b) some experimental tumour systems can be induced by chemical agents to differentiate to mature end-stage cells with no proliferative potential. Thus, it is conceivable that therapeutic agents can be developed which convert cancer cells to benign forms. To study the phenomenon of blocked maturation, squamous carcinoma SqCC/Y1 cells were employed in culture. Using this system it was possible to demonstrate that physiological levels of retinoic acid and epidermal growth factor were capable of preventing the differentiation of these malignant keratinocytes into a mature tissue-like structure. The terminal differentiation caused by certain antineoplastic agents was investigated in HL-60 promyelocytic leukaemia cells to provide information on the mechanism by which chemotherapeutic agents induce cells to by-pass a maturation block. The anthracyclines aclacinomycin A and marcellomycin were potent inhibitors of N-glycosidically linked glycoprotein biosynthesis and transferrin receptor activity, and active inducers of maturation; temporal studies suggested that the biochemical effects were associated with the differentiation process. 6-Thioguanine produced cytotoxicity in parental cells by forming analog nucleotide. In hypoxanthine-guanine phosphoribosyltransferase negative HL-60 cells the 6-thiopurine initiated maturation; this action was due to the free base (and possibly the deoxyribonucleoside), a finding which separated termination of proliferation due to cytotoxicity from that caused by maturation.
 ...
PMID:The 1985 Walter Hubert lecture. Malignant cell differentiation as a potential therapeutic approach. 389 54

Surface exposed membrane proteins of malignant cells may offer important clues about the differentiation stage of the cell or may contain proteins specific for the malignant state. We have studied the surface exposed membrane proteins of human acute myeloid leukemia cells employing the lactoperoxidase, periodate, or the neuraminidase/galactose oxidase ectolabeling procedures. One-dimensional membrane protein patterns were prepared from 20 patients, and from 19 patients, two-dimensional patterns were prepared according to O'Farrell. No consistent differences in membrane proteins could be found between patients classified as M1, M2, M4, or M5 (FAB classification). A diagram of membrane proteins from acute myeloid leukemia cells subjected to two-dimensional electrophoresis could be composed from the results obtained. About 25 different membrane proteins can be indicated. Two-dimensional patterns, after the various ectolabeling procedures, were also prepared from mature myeloid cells, visualizing about 18 different membrane proteins. Comparison of these and the undifferentiated myeloid leukemia cell pattern reveals some maturation-linked or leukemia-associated differences. The most relevant proteins will be discussed, along with their association with a recently described "malignancy marker" with a molecular weight of 68,000 daltons.
 ...
PMID:Two-dimensional membrane protein patterns of acute myeloid leukemia cells and mature myeloid cells after various ectolabeling procedures. 632 77

Pulsed nuclear magnetic resonance studies have been carried out on bone marrow of normal human subjects and patients with leukemia: chronic myeloid leukemia (CML) and acute myeloid leukemia (AML). It was observed that the proton spin-lattice relaxation time (T1) value was discriminatory in the normal and leukemic cases with a statistical significance of (p less than 0.01). Ouabain treatment of cells did not show any perceptible change of T1 value when compared with the nontreated cells, indicating that the concomitant cation effluxes do not affect spin-lattice relaxation time. The water contents of normal, leukemic, and ouabain treated cells were in the range 60%-80%. Higher Fe levels were encountered in the normal than the leukemic samples, while levels of Zn, Cu, Mn, Co, and Ni were elevated in the leukemic samples compared with the normals. Despite the T1 differences observed, the multiparameter studies do not uniquely pinpoint factors responsible for the elevation of T1 in the malignant state.
 ...
PMID:Distinction between normal and leukemic bone marrow by water protons nuclear magnetic resonance relaxation times. 696 35

The virally encoded oncogenes (v-onc) of avian and mammalian retroviruses are the recombinant products of normal cellular genes (c-onc) and a retroviral genome. These cellular homologues have been highly conserved during evolution and are found in human DNA. The expression of at least one c-onc under the control of a viral promoter results in transformation of cells in a manner resembling that displayed by the v-onc counterpart; the inappropriate expression of c-onc in the absence of viral influences could likewise result in the malignant state. This proposal would be strongly supported by the presence of c-onc RNAs in a variety of human tumours were they not also demonstrable in normal tissues. The role of these RNAs in the oncogenic process remains unclear. Here we report that RNA homologous to the oncogene (v-abl) of Abelson murine leukaemia virus (A-MLV) is expressed in a unique human leukaemia in a fashion different from that of other human tissues and tumours. In addition, DNA from this tumour transforms NIH-3T3 cells at a high efficiency in a transfection assay. The transfected sequences are not related to the v-abl gene, but the NIH-3T3 transformants manufacture a transforming growth factor which behaves similarly to factors produced by A-MLV-transformed NIH-3T3 fibroblasts.
 ...
PMID:Transforming gene of a human leukaemia cell is unrelated to the expressed tumour virus related gene of the cell. 712 5

The murine myelomonocytic cell line WEHI-3B exhibits ectopic expression of the genes encoding the homeobox protein, Hox-2.4, and the myeloid growth factor, interleukin-3 (IL-3). We showed previously that concomitant expression of IL-3 and Hox-2.4 in bone marrow cells induced the development of transplantable growth factor-independent tumours resembling the WEHI-3B tumour. We have now investigated the effect of enforced expression of Hox-2.4 alone. Bone marrow cells were infected with Hox-2.4 retrovirus and then either cultured in agar or transplanted into irradiated mice. In vitro, colonies derived from virus-infected cells readily yielded IL-3-dependent, non-tumorigenic cell lines of the myelomonocytic, megakaryocytic and mast cell lineages. Surprisingly, both the establishment and maintenance of these lines required very high concentrations of IL-3 and reduced levels promoted differentiation. Transplanted mice analysed after 3 months appeared normal but their spleen and bone marrow contained abundant provirus-bearing progenitor cells, from which IL-3-dependent long-term cell lines could readily be established in vitro. Four of 18 animals monitored for up to 12 months eventually developed clonal leukaemia, associated in three cases with IL-3 production. Thus ectopic expression of Hox-2.4 enhances self-renewal of immature myeloid progenitors and progression to a fully malignant state is favoured by somatic mutations conferring autocrine production of IL-3.
 ...
PMID:Conditional immortalization of mouse myelomonocytic, megakaryocytic and mast cell progenitors by the Hox-2.4 homeobox gene. 810 86


1 2 Next >>