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)

Friend mink cell focus-inducing virus (Fr-MCF) is a leukemogenic murine retrovirus that was isolated from a leukemic NIH Swiss mouse. We molecularly cloned the genome of this virus into pBR322. Restriction enzyme mapping of this cloned Fr-MCF DNA revealed a 1.0-kilobase-pair region in the envelope gene which differs from the restriction map of the Friend ecotropic virus (Friend murine leukemia virus). A 400-base-pair Fr-MCF envelope gene fragment was subcloned from this region and designated pLEK. Probes made with pLEK hybridize to Fr-MCF DNA but do not hybridize to either Friend or amphotropic murine leukemia virus DNA. Polyadenylic acid-selected RNA was prepared from the hematopoietic tissues of normal NIH Swiss mice, Fr-MCF-infected erythroleukemia cells (TP-1), and uninfected chemically transformed T lymphocytes (RB-1). The pLEK probe identified 34S and 22S messages in the TP-1 cells and in the normal hematopoietic tissues. RB-1 cells contain 32S and 26S messages that hybridize to pLEK. However, the pLEK-like RNAs found in the normal hematopoietic tissues and in the RB-1 cells were 400-fold less abundant than the RNAs found in the TP-1 cells.
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PMID:Molecular cloning of Friend mink cell focus-inducing virus: identification of mink cell focus-inducing virus-like messages in normal and transformed cells. 631 7

The earlier demonstration that genes of the mouse greatly influenced the spontaneous incidence of lymphoma was among the more persistent barriers to general acceptance of a viral etiology of this disease. We now can be fairly certain that some of those mouse genes are the DNA life phase of a class of retrovirus known as murine leukemia virus. These MuLV, although related in sequence to each other, are a collection of viruses that show diverse patterns of host range and tissue tropisms. The host-range properties of MuLV serve as means of classifying them into related families known as ecotropic, xenotropic, and amphotropic, and are probably dictated by determinants on gp70. The preferential abilities to replicate in different tissues, on the other hand, may be dictated by the controlling sequences located at the 3' end of the genome, known as U3. MuLV genomes are located at many different sites in the mouse genome. The viral genomes found at those sites can be induced to be expressed with different efficiencies spontaneously in vivo, by chemicals in vitro, or by DNA transfection. Certain MuLV genomes can also interact to increase expression perhaps by recombination or trans complementation. Although the molecular mechanisms that explain these phenomena are not yet clear, the phenomenon of differential expression has important pathological consequences, particularly in the development of lymphoma. The complex process by which endogenous MuLV induce leukemia appears to involve the expression and interaction of multiple MuLV genomes. It seems apparent that expression of an MCF-like gp70 is an invariant aspect of this process, and that observation suggests that this molecule, like the SFFV gp52, may indeed serve to stimulate cell proliferation. The most common means of expressing such a molecule at elevated levels appears to involve recombining it into an ecotropic genome that replicates with high efficiency. Thus, the viral requirements for leukemogenesis may depend on both efficient and perhaps tissue tropic replication as well as on the expression of a particular gp70.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Endogenous mouse leukemia viruses. 632 Jul 13

The myc oncogene is implicated here in T lymphocyte neoplasia. Cloning revealed a retroviral insert 0.7-1.3 kb 5' to c-myc in two T lymphomas induced by Soule murine leukemia virus and in a spontaneous T lymphoma ( Tikaut ) of an AKR mouse, a strain in which leukemogenesis involves recombinant retroviruses (MCF viruses). The tumor c-myc mRNAs appear normal but their level is approximately 5-fold higher than in most T lymphomas lacking c-myc rearrangement. Since each insert would be transcribed away from c-myc, its activation cannot involve the promoter of the long terminal repeat (LTR) but could reflect an enhancer, like that demonstrated within the Soule LTR. The Tikaut provirus has an MCF-like recombinant env gene and LTR sequence. MCF-like inserts were found near c-myc in seven of 31 other AKR T lymphomas; two lie 3' to c-myc and the five upstream are oriented away from c-myc. We conclude that a quarter of retrovirus-induced T lymphomas involve activation of c-myc, probably via the LTR enhancer.
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PMID:Murine T lymphomas in which the cellular myc oncogene has been activated by retroviral insertion. 632 47

Six new B lineage lymphomas of NFS mice established in primary tissue culture were examined for a number of phenotypic, functional, virologic, and molecular genetic characteristics. Two of the tumors and their cloned derivatives bore surface markers characteristic of B cells, whereas four tumors resembled pre-B cells. One of the B cell and two of the pre-B cell lymphomas had rearrangements of both heavy and light chain immunoglobulin genes, confirming their designation as B-lineage lymphomas. All the tumors but one were Ly-1+, indicating that Ly-1 may be expressed by some pre-B cells as well as some B cells. In addition, one pre-B cell lymphoma was Mac-1+. MCF murine leukemia viruses obtained from two of the tumors did not accelerate development of B-lineage lymphomas in NFS mice.
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PMID:A unique series of lymphomas related to the Ly-1+ lineage of B lymphocyte differentiation. 633 Feb 1

Tumour cells share with normal cells antigens characteristic of defined states of differentiation. Is there anything else? An example of tumour antigens not expressed anywhere in normal tissue is the set of tumour-specific transplantation antigens (TSTA) of murine chemically induced sarcomas. There is evidence that at least one TSTA specificity is retrovirus-derived, is carried on the envelope protein gp70, and probably arises by the recombination events that yield the diverse gp70s of the MCF strains of murine leukaemia viruses. Whether a similar mechanism can generate human tumour antigens depends on the yet unanswered question of whether human cells have retroviruses in their genomes capable of recombination. Aside from this, the only other mechanism known for antigen expression on tumours is via their oncogenes, which seem to make normal cell products. Such products, or secondary consequences of their production, were they normally expressed only at an early stage of development, would be candidates for 'fetal antigens'. While only the two mechanisms mentioned above seem the ready sources of 'tumour-associated antigens', it would be too early--in the face of ever more startling information about gene mobility and rearrangements--to think we have exhausted possible mechanisms for generating tumour antigens.
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PMID:How are tumour antigens related to normal antigens? 634 8

Stereoisomeric dichloro [1,2-bis(4-hydroxyphenyl)ethylenediamine]platinum(II) complexes (meso-3a, (+/-)-3b, (+)-3c, (-)-3d) and their N,N'-dibutyl derivatives (meso-4a, (+/-)-4b, (+)-4c, (-)-4d) were synthesized and tested on antitumor activity. The most active compound, 3d, shows a modest inhibition of the [3H]estradiol receptor interaction and causes a marked effect on the growth of the hormone-dependent human MCF 7 breast cancer cell line. It is also active on the hormone-independent human MDA-MB 231 breast cancer cell line, on the ADJ/PC6 plasmacytoma of the Balb/C mouse, and on the L 5222 leukemia of the BD IX rat. Apparently the inhibition of the MCF 7 cell line is not mediated by the estrogen receptor system. Histopathological studies on 3d revealed very low toxicity.
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PMID:Dichloro[1,2-bis(4-hydroxyphenyl)ethylenediamine]platinum(II) complexes: an approach to develop compounds with a specific effect on the hormone-dependent mammary carcinoma. 648 64

The presence of a gp66 closely related to the Friend ecotropic murine leukemia virus gp70 (F-MuLV) has recently been reported (D. Mathieu-Mahul, J. M. Heard, S. Fichelson, S. Gisselbrecht, B. Sola, and C. J. Larsen (1982) virology 119, 59-67). In the present work, characterization of this gp66 was continued. First, immunoprecipitation tests, using cytoplasmic membrane subfractions from one of the myelomonocytic cell lines in which gp66 was first detected, indicated that most of it was associated with rough endoplasmic reticulum. Second, to define the limits of gp66 expression, a variety of hemopoietic cell lines were analyzed for gp66 content. These lines were obtained (a) from various tumors (including erythroleukemias, chloroleukemias, and lymphatic leukemias) induced in susceptible mice by F-MuLV and (b) from long-term bone marrow cultures (LTBMC) infected with F-MuLV. In the latter case, lines of adherent fibroblastoid cells and nonadherent cells with myelomonocytic and mastocytic characteristics were obtained. Although several F-MuLV isolates were used, gp66 was only expressed in myelomonocytic and mastocytic cells. This did not result from in vitro culture conditions as gp66 was also found in fresh cells. These data suggested that a particular processing of the env gene product may exist in both myelomonocytic and mastocytic cell lines. In agreement with this hypothesis, a metabolically unstable gp62 related to MCF gp70 was found in one myelomonocytic cell line expressing MCF virus.
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PMID:The expression of the env gene-related gp66 in mouse cells infected with the helper independent Friend leukemia virus is restricted to the myelomonocytic and mastocytic lineages. 660 74

The recombinant (MCF) class of murine leukemia virus appears to play an important role in lymphomagenesis in AKR and other mice. Although much effort has been extended in characterizing MCF viruses, relatively little is known about the cells they infect. I examined what cells were targets in AKR mice for both lymphomagenic and nonlymphomagenic MCF viruses. Lymphomagenic MCF viruses of thymic origin (AKR-247 and C58L1) were found to infect and replicate selectively in immature lymphocytes only present in thymic cortex, whereas nonlymphomagenic MCF viruses of splenic origin (C58v-1-C77 and C58v-2-C45) selectively infected and replicated in cells that appeared to B lymphocytes. Virus-binding studies suggested that neither T- nor B-lymphocyte tropisms were determined by selective attachment of virus to the respective cells. These findings demonstrate that in contrast with ecotropic viruses, which can infect many types of cells in the mouse, specific cellular tropisms can exist for MCF viruses, and that MCF infection, and therefore oncogenicity, is closely linked to cellular differentiation.
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PMID:Characterization of target cells for MCF viruses in AKR mice. 668 36

A biologically active molecular clone of BALB/Moloney mink cell focus-forming (Mo-MCF) proviral DNA has been reconstructed in vitro. It contains the 5' half of BALB/Moloney murine leukemia virus (Mo-MuLV) DNA and the 3' half of BALB/Mo-MCF DNA. The complete nucleotide sequence of the env gene and the 3' long terminal repeat (LTR) of the cloned Mo-MCF DNA has been determined and compared with the sequence of the corresponding region of parental Mo-MuLV DNA. The substitution in the Mo-MCF DNA encompasses 1,159 base pairs, beginning in the carboxyl terminus of the pol gene and extending to the middle of the env gene. The Mo-MCF env gene product is predicted to be 29 amino acids shorter than the parental Mo-MuLV env gene product. The portion of the env gene encoding the p15E peptide is identical in both viral DNAs. There is an additional A residue in the Mo-MCF viral DNA in a region just preceding the 3' LTR. The nucleotide sequence of the 3' LTR of Mo-MCF DNA is similar to that of the 5' LTR of BALB/Mo-MuLV DNA with the exception of two single base substitutions. We conclude that the sequence substitution in the env gene is responsible for the dual-tropic properties of Mo-MCF viruses.
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PMID:Analysis of the env gene of a molecularly cloned and biologically active Moloney mink cell focus-forming proviral DNA. 714 66

The leukemogenic activity of Gross murine leukemia virus adapted to rats was tested in W/Fu rats and NIH/Swiss mice. All animals infected with this virus developed thymic and nonthymic T-cell leukemia with a short latency period. It was observed that cell-free extracts from thymic lymphoma tissue of mice and rats, induced by either Gross murine leukemia virus or Gross murine leukemia virus adapted to rats, consisted of both small-plaque-forming and large-plaque-forming viruses, as determined by the XC plaque test. MCF-type virus was found in these virus complexes. Transformed cell foci were induced in SC-1 cell layers by double infection of the cloned MCF-type virus and an ecotropic virus. SC-1 cells containing transformed cell foci were shown to be tumorigenic upon inoculation into nude mice. The formation of transformed cell foci in mink lung cells was also observed after double infection with the cloned MCF-type virus and a xenotropic virus. The possible mechanism of leukemogenesis by endogenous viruses is discussed.
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PMID:Leukemogenicity and cell transformation mechanisms in vitro by Gross murine leukemia virus: analysis of virus subpopulations. 724 57


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