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)

Nine cases have been presented in detail to illustrate some of the varied causes of sudden neurological deficit in childhood: arteriovenous malformation, cryptic hamartoma, berry aneurysm, mycotic aneurysm, intraspinal arteriovenous malformation, brain tumor, migraine, arteritis, and multiple sclerosis. The Boston Children's Hospital experience with aneurysms and intracranial arteriovenous malformation has been summarized. It is noteworthy that a cutaneous hemangioma overlay one cranial and one intraspinal arteriovenous malformation. One small but deep cerebral arteriovenous malformation apparently destroyed itself after its second hemorrhage. Not only have multiple sclerosis and a brain tumor mimicked a vascular lesion, but a series of vascular accidents was misdiagnosed first as multiple sclerosis then as a thalamic tumor. The many possible causes of childhood strokes has been thoroughly cataloged in the Report of the Joint Committee for Stroke Facilities in 1973 (11). Children may be more susceptible to strokes because of congenital abnormalities such as congenital heart disease, hemophilia, and sickle cell anemia, or by diseases which more commonly occur in this age group, such as leukemia. The likelihood of brain abscess in cyanotic congenital heart disease is stressed. Arteriographic studies in our series have been safe; however, there have been reports of probable worsening of symptoms in children with multiple cerebral occlusive lesions in the presence of homocystinuria.
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PMID:Strokes in children. 98 45

The expression of murine leukemia provirus in embryonal carcinoma (EC) cells is blocked by a mechanism still incompletely understood. The blockage is not overcome by deleting a large portion of the enhancer region (in U3) in recombinant retroviruses (M-MuLVneo delta Enh). This confirms the presence of negative elements outside the viral 82-bp repeats. However, a few sites in the genomes of EC cells permit M-MuLVneo delta Enh proviral expression. One such site, identified in PCC4, PCC3, and LT, was studied. The complete analysis of the mechanism of activation by Northern (RNA) blotting, cloning, and sequencing of partial cDNA copies of the viral transcript and of the site of integration establishes that viral transcripts are initiated from an upstream host-cell promoter and are spliced from a host donor to a cryptic viral acceptor at position 542 in the Moloney murine leukemia virus (M-MuLV) genome. In consequence, the mature transcripts are host cell-virus fusion transcripts from which M-MuLV sequences, including the cis-active negative elements of the 5' long terminal repeat-containing region, are absent. The provirus integrates apparently randomly into any of the three most proximal introns of the transcriptional unit. The host cell promoter contains a TATA box and 14 potential SpI binding sites included in a 1.0-kb GC-rich island. These elements promote gene expression of recombinant vectors in EC and differentiated cells. The mechanism described points to a mechanism by which retroviruses can be transcribed from upstream nonviral elements and can acquire host genes by 5' annexation of exons.
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PMID:Capture of a cellular transcriptional unit by a retrovirus: mode of provirus activation in embryonal carcinoma cells. 132 Dec 82

In this report we describe two newly isolated pre-B acute lymphoblastic leukaemia cell lines. Both cell lines lack EBV as detected by the EBNA-1 gene probed Southern-blots. Neither cell line expressed the B-cell-specific CD20 antigen on the cell membrane. However surface expression of CD20 was induced by phorbol ester (TPA) on both LiLa-1 and LK63 cell lines. Other pre-B and B-cell lines, such as Reh, Nalm-1, and BALL-1 did not exhibit these changes in phenotype. Previous immunoprecipitation studies have noted that a broad 50-55 kD band co-precipitates with the characteristic 33-37 kD CD20 protein. We demonstrate that, while the 33-37 kD CD20 species was undetectable on resting LiLa-1 and LK63 cells, in each case a 50-55 kD protein was immunoprecipitated by the CD20 antibody. However, the failure to detect any cell surface CD20-associated antigen on the control cells by immunophenotyping indicated that the CD20 epitope of the 50-55 kD molecule was not expressed on the cell surface. Following exposure to TPA the 50-55 kD species was reduced over 48-72 h while the level of the p33-37 CD20 protein was increased. Northern-blot analysis showed that the 50-55 kD protein was not a cryptic form of CD20 as the uninduced cells contained no detectable CD20 mRNA. The decrease of the 50-55 kD protein and the acquisition of the mature CD20 molecule were paralleled by a decline in proliferative activity in both cell lines. As expression of CD20 by normal pre-B cells also coincides with the cessation of cell division and maturation towards a mature B-cell phenotype, these cell lines appear to represent models for a discrete stage of B-cell differentiation which may be valuable in defining the signals regulating pre-B-cell proliferation.
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PMID:Characterization of two novel pre-B-cell lines (LK63 and LiLa-1): potential models of pre-B-cell differentiation. 137 17

Expression of the normally cryptic blood group antigen Tn has occasionally been reported in hematologic disease, but the true frequency of this change is not known. A mouse monoclonal antibody (FBT3) and immunohistochemistry were used to examine expression of the Tn antigen. Expression was not detected in 35 normal bone marrow aspirates examined, but it was detected in 5 of 725 abnormal bone marrow aspirates, including 2 (3.6%) of 55 cases of de novo acute nonlymphocytic leukemia and 2 cases that terminated in acute nonlymphocytic leukemia. In two patients, one with acute myeloblastic leukemia and the other in blast transformation of chronic myeloid leukemia, the Tn antigen was expressed on 2 percent of blast cells. In one case of non-Hodgkin's lymphoma, 4 percent of normal myeloid cells expressed the antigen. In the other two cases, one of acute myelomonocytic leukemia and the other of myelodysplasia, only 2 to 8 percent of myeloid and erythroid cells initially were Tn positive. Subsequent serial immunohistochemical studies of bone marrow aspirates and peripheral blood in these two cases showed increasing numbers of Tn-positive erythroid and myeloid cells 8 to 12 months before polyagglutination was detected serologically. Tn-positive cells increased to > 90 percent in the terminal phase in both cases of both diseases. The results suggest that Tn expression in these two patients may have conferred a growth advantage to the cells and could be related to disease progression.
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PMID:Expression of the Tn antigen in myelodysplasia, lymphoma, and leukemia. 147 Dec 47

An increasing number of papers document cases of acute leukemia in which individual blast cells co-express markers normally restricted to a single cell lineage. Numerous terms are used to refer to cases with unscheduled expression of lineage-foreign proteins; the best defined categories were hybrid acute leukemia and acute mixed-lineage leukemia. The incidence of phenotypically variant acute leukemia varies with the quality and quantity of parameters used and the stringency of the criteria employed for its definition. Considerable interest has focused on acute lymphoblastic leukemia (ALL) cells expressing one or several myeloid lineage-associated antigens (My+ ALL), CD13, CD14, CD15, CD33, and CDw65. Owing to legitimate and cryptic expression on lymphoid cells, CD11b and CD15 reagents may not be considered as specific indicators of myeloid differentiation. The reported incidence ranged from 5 to 46% in 14 studies on My+ ALL, totalling 3817 patients. Several detailed reports documented a higher incidence of My+ ALL in adults (realistically in the range 10-20%) than in children (5-10%) and in B-lineage ALL as opposed to T-lineage ALL. My+ ALL cases are more likely to display unique cytogenetic [t(9;22), 11q23, 14q32] features than My-neg ALL. There appears to be no predominant expression of a single myeloid-associated antigen among those analyzed. As the morphological diagnosis of a leukemia subtype is often imprecise, some T-neg B-neg My+ ALL cases might actually contain FAB AML-M0 populations. While the expression of myeloid-associated antigens has no apparent prognostic significance in the majority of childhood ALL subtypes, in adults myeloid antigens seem to identify a high risk group of ALL patients with a poorer response to standard ALL therapy.
Leukemia 1991 Aug
PMID:Review of the incidence and clinical relevance of myeloid antigen-positive acute lymphoblastic leukemia. 188 19

Proviral DNA derived from a recombinant retroviral vector (LHMlPL), constructed to transduce the human purine nucleoside phosphorylase coding region along with the mouse metallothionein l promoter, was molecularly cloned in order to characterize a deletion previously observed in this provirus. Nucleotide sequence comparison with the original retroviral vector construct revealed two deletions in the cloned provirus. One of the deleted regions originated entirely from within the mouse metallothionein promoter. A second deletion eliminated portions of both viral and metallothionein promoter sequences. All four deletion junctions in the original construct included sequences which conform to those proposed as eukaryotic consensus splice donor and acceptor signals, including a previously unreported cryptic splice donor signal in the Moloney leukemia virus envelope gene. It is concluded that RNA splicing between inadvertently juxtaposed donor and acceptor signals was responsible for the observed deletions.
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PMID:Deletion in a recombinant retroviral vector resulting from a cryptic splice donor signal in the Moloney leukemia virus envelope gene. 211 58

We have examined splice site activation in relation to intron structure in murine sarcoma virus (MuSV)-124 RNA. MuSV-124 contains inactive murine leukemia virus env gene splice sites (termed 5' env and 3' env) as well as cryptic sites in the gag and v-mos genes (termed 5' gag and 3' mos) which are activated for thermosensitive splicing by a 1,487-base intronic deletion in the MuSV-124 derived MuSVts110 retrovirus. To determine conditions permissive for splice site activation, we examined MuSV-124 mutants deleted in the 1,919-base intron bounded by the 5' gag and 3' mos sites. Several of these deletions activated thermosensitive splicing either at the same sites used in MuSVts110 or in a previously unreported temperature-sensitive splice event between the 5' gag and 3' env sites. These data suggested that the thermosensitive splicing phenotype characteristic of MuSVts110 required neither a specialized intron nor selection of a particular 3' splice site. The 3' env and 3' mos sites were found to compete for splicing to the 5' gag site; the more upstream 3' env site was exclusively used in MuSV-124 mutants containing both sites, whereas selection of the 3' mos site required removal of the 3' env site. Branchpoint sequences were found to have a potential regulatory role in thermosensitive splicing. Insertion of a beta-globin branchpoint sequence in a splicing-inactive MuSV-124 mutant activated efficient nonthermosensitive splicing at the 3' mos site, whereas a mutated branchpoint activated less efficient but thermosensitive splicing.
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PMID:Activation of cryptic splice sites in murine sarcoma virus-124 mutants. 217 Jun 71

Two murine monocytic leukemia cell lines, WEHI-265 and WEHI-274, were found to carry a rearranged c-myb gene. The rearrangements are due to insertion of a deleted Moloney murine leukemia virus (Mo-MLV) provirus in the 5' region of the c-myb gene and thus are similar to rearrangements in the ABPL tumors (G. L. C. Shen-Ong, M. Potter, J. F. Mushinski, S. Lavu, and E. P. Reddy, Science 226:1077-1080, 1984). In each cell line, the retroviral insertion has induced high levels of two aberrant RNA species, which, as in the ABPL tumors (G. L. C. Shen-Ong, H. C. Morse, M. Potter, and J. F. Mushinski, Mol. Cell. Biol. 6:380-392, 1986), contain both viral (Mo-MLV) and cellular (myb) sequences. Both species lack the sequences encoding the amino terminus of the c-myb protein and thus could encode a protein which, like the v-myb gene products (and the predicted ABPL myb proteins), is truncated at the amino terminus. We have found that the larger (5.3 kilobase [kb]) and more abundant of the tumor-specific myb RNAs was predominantly nuclear, while the smaller species (3.9 kb) was cytoplasmic. Furthermore, our data imply that the 3.9-kb RNA was derived from the 5.3-kb RNA by an additional splice which utilized a cryptic splice acceptor site within the viral gag sequences. On the basis of subcellular distribution and predicted translational potential, we conclude that the 3.9-kb RNA is probably the mRNA which encodes a truncated myb protein. We also show that, due to different insertion points in W265 and W274, the W274 myb RNAs contained sequences from a c-myb exon upstream of the exons represented in the W265 (and ABPL) RNAs. The significance of our findings with regard to transformation by myb in these tumors is discussed.
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PMID:Generation of altered transcripts by retroviral insertion within the c-myb gene in two murine monocytic leukemias. 244 Oct 77

Two modes of disruption of the protooncogene c-myb by viral insertional mutagenesis in mouse myeloid tumor cells are described. The first mode was found in six tumors in which a Moloney murine leukemia virus component had inserted in the same transcriptional orientation upstream of the 5'-most exon with v-myb homology (vE1). cDNA sequence data indicate the presence of a truncated c-myb mRNA that is initiated in the upstream 5' long terminal repeat of the integrated provirus and processed via a cryptic splice donor sequence in the gag region to the splice acceptor site in vE1 of the c-myb gene, thus removing the remaining downstream viral and myb intronic sequences. Unlike most gag-onc transcripts, the gag and myb sequences in the hybrid transcript were not in the same reading frame. It is presumed that the gag sequence provides a cryptic translation initiation site for the novel amino-truncated c-myb protein. The second mode of disruption was by downstream virus insertion at the 3' side of the c-myb, which results in the synthesis of a small (approximately 2 kilobase) myb transcript. The 5' long terminal repeat of the inserted provirus provides a TGA termination codon that results in the elimination of 240 normal c-myb amino acid residues from the carboxyl terminus of the tumor-specific myb protein. These results suggest that truncated myb proteins play a role in neoplastic transformation of myeloid cells.
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PMID:Two modes of c-myb activation in virus-induced mouse myeloid tumors. 302 43

Whereas it is generally believed that most cases of hairy cell leukaemia (HCL) represent B cell neoplasms, it is reported here that 4 of 14 cases of HCL not only express monotypic surface immunoglobulin (SIg) but also react with the T cell-specific monoclonal antibody (Mab) UCHT1 by indirect immunofluorescence or immunoperoxidase staining. Although both UCHT1 and OKT3 recognize the T3 molecule, which is expressed in all normal T cells, UCHT1+ hairy cells (HCs) were consistently OKT3-. Spurious reactivity of UCHT1 antibodies with SIg+ HCs was excluded by showing that lymphocytes sensitized with an irrelevant mouse Mab did not stain with second layer antibodies and lymphocytes sensitized with second layer antibodies alone were always completely unreactive. Moreover, in 1 case the determinants demonstrable by both UCHT1 and anti-Ig were strongly re-expressed after capping and shedding, i.e. appeared to be endogenous. It is concluded that HCs with a hybrid T-B surface phenotype are more common than hitherto reported, that HCs may express T3 molecules as well as SIg but that determinants recognized by OKT3 may be cryptic or buried in the HC membrane.
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PMID:Co-expression of surface immunoglobulin and T3 on hairy cells. 309 6


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