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)

The DNA obtained from the leukemia cells of an acute lymphoblastic leukemia (ALL, L3 type) with a pre-B-phenotype and a typical t(8;14) chromosomal translocation showed a rearrangement juxtaposing the c-myc gene and the immunoglobulin (Ig) heavy-chain gene enhancer. This abnormality was only present in the leukemia cells of the patient and correlated with the clinical course of the disease. The breakpoint on chromosome 8 occurred within c-myc intron 1, between 790 and 638 base pairs upstream of c-myc exon 2. This breakpoint position was the nearest to the c-myc exon 2 so far described in Burkitt's type lymphoma-leukemias, and it mapped very near to the location of a major cryptic promoter used by truncated c-myc genes. In spite of what was detected in a human lymphoma cell line (Manca) carrying a similar rearrangement, in this case the amount of c-myc transcript was not increased compared to an Epstein-Barr virus-transformed normal lymphoblastoid cell line obtained from the same patient. This may in part be due to the breakpoint position and to the fact that the efficiency of the major cryptic promoter present within the first intron could have been affected by the translocation event. Finally, as previously suggested by others, the phenotype expressed by the leukemia cells supported the notion that this particular type of rearrangement (linking together the c-myc gene and the Ig heavy-chain gene enhancer element) may be associated with a subgroup of B-ALLs showing an immunologic phenotype relatively more immature than that of classical B-ALL.
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PMID:Rearrangement of the c-myc oncogene with heavy-chain immunoglobulin enhancer in tumor DNA from an acute lymphoblastic leukemia patient. 310 93

Normal and malignant myeloid cells express a highly immunogenic oligosaccharide, lacto-n-fucopentaose-III (LNF-III), that has been identified by numerous monoclonal antibodies (MoAb). We have been interested in the use of a particular monoclonal antibody to LNF-III, PM-81, in the treatment of patients with acute myelogenous leukemia using the antibody to treat bone marrow in vitro. Following in vitro treatment of bone marrow with PM-81 and another MoAb, AML-2-23, the remaining cells are used as an autograft in a patient treated with high-dose chemotherapy and radiotherapy. In order to enhance the ability of the MoAb to lyse leukemic cells in the remission bone marrow, we have explored the effect of neuraminidase treatment on leukemia cells. In this paper we describe that myeloid leukemia cells expressing low levels of LNF-III by immunofluorescence can be shown to have high levels of LNF-III after neuraminidase treatment. In addition, we show that normal bone marrow progenitor cells do not have cryptic LNF-III antigen, thus allowing the application of this finding to the clinical setting. Moreover, we have shown that leukemia colony-forming cells from one patient with acute myelogenous leukemia express cryptic LNF-III and that after exposure to neuraminidase there was an increased ability of PM-81 in the presence of complement to eliminate these colony forming cells. These data indicate that the LNF-III moiety is almost universally expressed on myeloid leukemia cells and their progenitors but not expressed on normal progenitors. Thus, it may be possible to enhance leukemia cell kill in vitro by neuraminidase treatment of bone marrow.
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PMID:Monoclonal antibodies to carbohydrate antigens in autologous bone marrow transplantation. 328 49

Exposure of the normally cryptic Tn antigen on haemopoietic cells leading to erythrocyte polyagglutination has been reported in a few cases of malignant or premalignant haemopoietic disorders and has been attributed to a selective deficiency of the enzyme 3-beta-D-galactosyl-transferase. A male patient presented with acute myelomonocytic leukaemia with no evidence of Tn expression but, 16 months later, in the terminal stage of the disease, the majority of the erythrocytes were found to be polyagglutinable. Tn expression was confirmed by the use of lectins and by agglutination with a Tn-specific monoclonal antibody, FBT3. Retrospective studies of stored blood and bone marrow smears were performed by immunocytochemistry using FBT3. Tn positive cells were first detected in the marrow 8 months prior to death. They increased progressively in number and, in the terminal illness, over 90% of erythroid precursors in the marrow and erythrocytes in peripheral blood and 40% of granulocyte precursors of the marrow and 10% of granulocytes in the blood were Tn positive. These observations suggest that Tn expression was present in a subclone of cells which became dominant during the course of the disease and that there may be a relationship between Tn expression and leukaemic progression.
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PMID:Detection of the Tn antigen in leukaemia using monoclonal anti-Tn antibody and immunohistochemistry. 347 88

p56lck is a new member of the src family of cellular tyrosine protein kinases. It is expressed constitutively at a low level in normal T cells and at an elevated level in the LSTRA and Thy19 Moloney murine leukemia virus-induced thymoma cell lines. It is possible that the expression of p56lck at an elevated level contributes to the transformation of these thymoma cells. The structure of the mRNAs encoding p56lck was examined by using an RNase protection assay. Both a chimeric lck mRNA containing the 5' untranslated region of Moloney virus mRNA and a normal lck mRNA were found in Thy19 and LSTRA cells. The chimeric lck transcript was 4- to 10-fold more abundant than the normal transcript. Transcription arising from a viral promoter is therefore responsible for the elevated levels of lck mRNA in these two cell lines. Surprisingly, uninfected murine T cells were also found to contain lck transcripts with differing 5' untranslated regions. One species of mRNA was colinear with the region of the chromosome just upstream of the initiation codon for p56lck. The other appeared to arise through splicing of an unidentified 5' untranslated exon to a sometimes cryptic splice acceptor just upstream of the region encoding p56lck. These data suggest that lck is expressed through the use of at least two different promoters. The promoters could be subject to different forms of regulation.
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PMID:Two lck transcripts containing different 5' untranslated regions are present in T cells. 350 24

The nucleotide sequence of a 5' segment of the human genomic c-fms proto-oncogene suggested that recombination between feline leukemia virus and feline c-fms sequences might have occurred in a region encoding the 5' untranslated portion of c-fms mRNA. The polyprotein precursor gP180gag-fms encoded by the McDonough strain of feline sarcoma virus was therefore predicted to contain 34 v-fms-coded amino acids derived from sequences of the c-fms gene that are not ordinarily translated from the proto-oncogene mRNA. The (gP180gag-fms) polyprotein was cotranslationally cleaved near the gag-fms junction to remove its gag gene-coded portion. Determination of the amino-terminal sequence of the resulting v-fms-coded glycoprotein, gp120v-fms, showed that the site of proteolysis corresponded to a predicted signal peptidase cleavage site within the c-fms gene product. Together, these analyses suggested that the linked gag sequences may not be necessary for expression of a biologically active v-fms gene product. The gag-fms sequences of feline sarcoma virus strain McDonough and the v-fms sequences alone were inserted into a murine retroviral vector containing a neomycin resistance gene. Both constructs were biologically active when transfected into NIH 3T3 cells and produced morphologically transformed foci at equivalent efficiencies. When transfected into a cell line (psi 2) expressing complementary viral gene functions, G418-resistant (Neor) cells containing either of these vector DNAs produced high titers of transforming viruses. Analysis of proteins produced in cells containing the vector lacking gag gene sequences showed that gP180gag-fms was not synthesized, whereas normal levels of both immature gp120v-fms and mature gp140v-fms were detected. The glycoprotein was efficiently transported to the cell surface, and it retained wild-type tyrosine kinase activity. We conclude that a cryptic hydrophobic signal peptide sequence in v-fms was unmasked by gag deletion, thereby allowing the correct orientation and transport of the v-fms gene product within membranous organelles. It seems likely that the proteolytic cleavage of gP180gag-fms is mediated by signal peptidase and that the amino termini of gp140v-fms and the c-fms gene product are identical.
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PMID:The amino-terminal domain of the v-fms oncogene product includes a functional signal peptide that directs synthesis of a transforming glycoprotein in the absence of feline leukemia virus gag sequences. 352 54

The genome of Kirsten murine sarcoma virus was formed by recombination between Kirsten murine leukaemia virus sequences, and rat sequences derived from a retrovirus-like '30S' (VL30) genetic element encompassing the Kras oncogene. Using cloned DNAs we have determined the nucleotide sequences of the long terminal repeats and adjacent regions, extending across the points of recombination on the sarcoma and leukaemia virus genomes. Our results suggest that discrete regions of homology and other cryptic sequence features, may have constituted recombinational hot-spots involved in the genesis of the Kirsten murine sarcoma virus genome. We have also compared the sequence of the Kirsten murine leukaemia virus p15 env and adjacent long terminal repeat with the corresponding regions of the AKV and Gross A murine leukaemia virus genomes. This comparison has identified a leukaemogenic determinant in the U3 domain of the long terminal repeat, possibly within a enhancer-like sequence element.
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PMID:Genesis of Kirsten murine sarcoma virus: sequence analysis reveals recombination points and potential leukaemogenic determinant on parental leukaemia virus genome. 609 Oct 40

We studied the effects of murine leukemia virus infection on the growth of tumors in inbred strain 2 guinea pigs. Fibrosarcomas, induced by treatment of guinea pig fetal cells with chemical carcinogens, were exposed in vitro to the amphotropic murine leukemia virus, 4070A. Tumor cells exposed to murine leukemia virus 4070A in vitro expressed virus antigens, released both reverse transcriptase and infectious virus into supernatant fluids, and grew and regressed after injection into syngeneic animals. In contrast, uninfected tumor cells did not express virus antigens and grew progressively. Rejection of virus-infected tumor cells appeared to be a host-mediated event, since murine leukemia virus 4070A infection had no detectable cytopathic effect on fibrosarcoma cells. Rejection of virus-infected tumor cells occurred in guinea pigs unable to suppress the growth of the line 10 hepatoma at sites of injection of mycobacterial cell walls and unable to develop immunity to the line 10 hepatoma. Guinea pigs immunized with virus-infected tumor cells were unable to reject a challenge of uninfected tumor cells. The results are interpreted to mean that infection of guinea pig tumors in vitro by a murine leukemia virus led to synthesis of viral antigens by the tumor cells which in turn led to recognition of the tumor as foreign with consequent tumor destruction; tumor eradication occurred without development of immunity to cryptic, intrinsic tumor antigens.
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PMID:Tumor rejection mediated by an amphotropic murine leukemia virus. 618 93

Human acute lymphoblastic leukemia cell lines represent valuable tools to investigate distinct steps of the complex regulatory pathways underlying T cell receptor recombination and expression. A case in point are V delta 2D delta 3 and subsequent V delta 2D delta 3J alpha rearrangements observed in human leukemic pre-B cells as well as in normal lymphopoiesis. The functional expression of these unusual (VD) delta (JC) alpha hybrids is almost exclusively prevented by alternative splicing events. In this report we show that alternative splicing at cryptic splice donor sites within V elements is not a unique feature of hybrid TCR delta/alpha transcripts. Among seven V alpha families analyzed by RT-PCR, alternatively spliced products were observed in TCR alpha recombinations containing V alpha 1 or V alpha 14 elements. In contrast to normal peripheral blood cells and thymocytes, the leukemia cell line JM expressing functional V alpha 1J alpha 3C alpha transcripts lacked evidence of aberrant TCR alpha RNA species.
Leukemia 1995 Oct
PMID:Alternative splicing of T cell receptor (TCR) alpha chain transcripts containing V alpha 1 or V alpha 14 elements. 756 13

Induction of apoptosis is the molecular basis for the therapeutic application of glucocorticoids (GC) in human leukemia. The beneficial effect of endocrine therapy is, however, hampered by the occurrence of resistant clones evolving under selective GC pressure. To delineate molecular mechanisms of GC resistance, we PCR amplified, cloned, and sequenced GC receptor (GR) transcripts and gene segments from a GC-resistant subclone of the human acute leukemic cell line CCRF-CEM, termed CEM-R6. Our analyses revealed that one GR gene allele harbored a point mutation (L753F) previously shown to compromise GR functions in other CCRF-CEM derivatives. On the second allele, we identified an A to G point mutation in the 3'-splice junction of intron G. As a consequence, a cryptic splice site 8 base pairs downstream within exon 8 is recognized, which leads to an 8-base deletion in the GR mRNA, resulting in reading frame shift and 2 consecutive in-frame preterminal stop codons. Translation of this mutant mRNA would produce a truncated GR protein missing 93 amino acids of the ligand-binding domain and expressing 9 altered residues at its new COOH terminus. In concert with the L753F mutation on the other allele, this molecular defect explains the GC-resistant phenotype and provides further evidence for mutational GR gene inactivation as a mechanism for human leukemic cells to escape GC-induced apoptosis.
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PMID:Splice site mutation in the glucocorticoid receptor gene causes resistance to glucocorticoid-induced apoptosis in a human acute leukemic cell line. 781 67

Cytogenetic analysis of unstimulated bone marrow (BM) and peripheral blood (PB) cells of a patient with clinical features of atypical chronic myeloid leukemia (CML) showed t(12;22)(p13;q12) as the sole karyotypic abnormality. Subsequent fluorescence in situ hybridization (FISH) with abl- and bcr-specific cosmids as well as chromosome 12- and 22-specific DNA libraries and Southern blot analysis confirmed that in this patient t(12;22) does not constitute a cryptic Ph variant. Recently, a few very similar cases were reported by other investigations. The possible significance of this translocation as a new cytogenetic marker for nonlymphocytic leukemia is discussed.
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PMID:Translocation (12;22)(p13;q12) as sole karyotypic abnormality in a patient with nonlymphocytic leukemia. 814 67


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