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 vast majority of pediatric RBC hypoplastic anemias are accounted for by red blood cell aplasia associated with chronic hemolysis, Diamond-Blackfan anemia, and transient erythroblastopenia of childhood. However, other causes of hypoplastic anemia occur in children, and some of these are similar to what is seen in adult RBC aplasia. For example, it has been reported that a 5-year-old girl with an aregenerative anemia had a thymoma and later developed pancytopenia. RBC aplasia also has been seen in children receiving anticonvulsant drug therapy, children recovering from severe protein malnutrition, children with hepatitis, and in children with leukemia during maintenance therapy. In addition, it is not uncommon for pediatric hematologists to observe children with RBC aplasia where there is no obvious diagnosis, although many are considered to be variants of Diamond-Blackfan anemia. Several important questions about RBC hypoplastic anemias in children need to be resolved; it is hoped that this will be accomplished in the next decade. Do RBC hypoplastic crises associated with hemolytic anemia occur with viral infections other than HPV? What is the cellular pathophysiology in DBA and TEC? Does the apparent heterogeneity of these disorders reflect limitations of laboratory techniques or are we looking at several different diseases? Is acute leukemia a real complication of Diamond-Blackfan anemia? Is TEC a completely benign entity or will we see other long-term problems in these children? Is the incidence of TEC actually increasing? Will TEC-like problems be seen in other aged children? As a case in point, we recently observed a 16-year-old girl who presented with pure RBC aplasia that required RBC transfusion support for 5 months; she also received prednisone therapy. After 7 months, however, this young lady had a spontaneous remission, and now 4 years later she is normal and free of any hematologic abnormalities. This was a most unusual event in our experience and, in view of the apparent increasing incidence of TEC in young children, we queried whether we were observing an adolescent equivalent of this disorder. During the next several years the answer to this and the other questions posed herein should be available.
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PMID:Diagnosis and management of red cell aplasia in children. 312 94

Newborn germ-free (GF) and conventional (CV) BALB/c mice were infected with murine leukemia virus-Moloney (MuLV-M) and subsequently monitored for virus expression and leukemia development. GF mice expressed more than 10-fold less virus in peripheral blood compared with CV mice, despite equivalent numbers of infected cells in the spleens, lymph nodes, thymi, and bone marrow of both groups. In addition to lower levels of virus expression, the latency period before the onset of fatal leukemias was greatly extended in GF mice; the first and last fatalities were recorded at 25 and 43 weeks postinfection, respectively, with a mean survival time of approximately 36 weeks. In CV mice, the first and last fatalities occurred at 8 and 17 weeks, respectively, with a mean survival time of approximately 13.5 weeks. Finally, the gross pathology of involved lymphoid organs varied in the two groups. GF mice experienced severe splenomegaly with or without lymphadenopathy but without thymoma; CV mice, in contrast, developed splenomegaly, lymphadenopathy, and severe thymoma. Collectively, these results indicate a marked resistance of GF animals to MuLV-M and suggest that the level of immune system activation may influence the pathogenicity of nontransforming retroviruses.
Leukemia 1988 Aug
PMID:Decreased pathogenicity of murine leukemia virus-Moloney in gnotobiotic mice. 326 22

Of 17 Moloney murine leukemia virus (MoMuLV)-induced rat thymomas, 2 contained rearrangements in c-myc. In one of these tumors the observed rearrangement was not due to the insertion of an intact MoMuLV provirus. The rearranged c-myc DNA fragment from this thymoma was cloned and examined by restriction endonuclease mapping, hybridization to MoMuLV proviral DNA probes, and DNA sequence analysis. These analyses revealed that the c-myc rearrangement in this tumor was due to the presence of a partially duplicated MoMuLV long terminal repeat (LTR) 5' to c-myc exon 1. The orientation of this LTR structure was opposite to the transcriptional orientation of c-myc. The sequences at the 3' flanking side of the LTR structure were derived from a cellular DNA region which maps to the same chromosome as c-myc (chromosome 7), although to a site distant from this proto-oncogene. These findings present evidence for a homologous recombination event occurring between sequences of two proviruses integrated on the same chromosome, one of which was inserted near the c-myc proto-oncogene. The recombination product contains three copies of the MoMuLV LTR 72-base-pair direct repeat and is associated with a high level of c-myc expression. The reciprocal product of this recombination was not detected. We propose that recombination between homologous sequences may play a significant role in the generation of chromosomal rearrangements and therefore in tumor induction and progression.
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PMID:Recombination between two integrated proviruses, one of which was inserted near c-myc in a retrovirus-induced rat thymoma: implications for tumor progression. 327 24

We report the isolation and nucleotide sequence of a 3.7-kilobase (kb) cDNA clone from chicken spleen corresponding to a previously undescribed member of the src family of protooncogenes. It encodes a protein with a C-terminal domain related to the src family of protein-tyrosine kinases (EC 2.7.1.112) and, among these, has most significant homology to the lck gene isolated from a murine leukemia virus-induced thymoma cell line. The gene is therefore referred to as c-tkl for cellular tyrosine kinase related to lck. Analysis of genomic DNA reveals that c-tkl is a chromosomal locus distinct from c-src and c-lck. Furthermore, the size of c-tkl mRNA as well as its pattern of expression indicates that it is not the chicken homologue of lck but a different gene. A 3.8-kb transcript of the c-tkl gene, identical to the size determined for c-src mRNA, was observed in cultured chicken embryo fibroblasts and in chicken spleen and brain. In contrast, detection of a definite c-src mRNA signal with mRNA from spleen was not possible under the hybridization conditions employed when the 5' end of v-src was used as the probe, and none of the 11 clones obtained from the cDNA library corresponded to a c-src transcript. Thus previous studies of c-src mRNA expression in spleen may have actually detected c-tkl transcripts.
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PMID:Additional member of the protein-tyrosine kinase family: the src- and lck-related protooncogene c-tkl. 332 Oct 53

Seven cellular loci with acceptor sites for retroviral integrations have been mapped for the presence of DNase I-hypersensitive sites in chromatin. Integrations in three of these loci, chicken c-erbB, rat c-myc, and a rat locus, dsi-1, had been selected for in retrovirus-induced tumors. Of the remaining four, two, designated dsi-3 and dsi-4, harbored acceptor sites for apparently unselected integrations of Moloney murine leukemia virus in a Moloney murine leukemia virus-induced thymoma, and two, designated C and F, harbored unselected acceptor sites for Moloney murine leukemia virus integrations in a rat fibroblast cell line. Each acceptor site mapped to within 500 base pairs of a DNase I-hypersensitive site. In the analyses of the unselected integrations, six hypersensitive sites were observed in 39 kilobases of DNA. The four acceptor sites in this DNA were localized between 0.05 and 0.43 kilobases of a hypersensitive site. The probability of this close association occurring by chance was calculated to be extremely low. Hypersensitive sites were mapped in cells representing the lineage in which integration had occurred as well as in an unrelated lineage. In six of the seven acceptor loci hypersensitive sites could not be detected in the unrelated lineage. Our results indicate that retroviruses preferentially integrate close to DNase I-hypersensitive sites and that many of these sites are expressed in some but not all cells.
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PMID:Acceptor sites for retroviral integrations map near DNase I-hypersensitive sites in chromatin. 349 May 82

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

Many highly homologous genes are present in the murine major histocompatibility complex (MHC) class I gene family. Consequently, it is difficult to distinguish between RNA transcripts of individual class I genes solely on the basis of nucleic acid hybridization analysis using DNA probes over 50 base pairs long. To avoid this problem, I have designed and synthesized a set of oligonucleotide probes capable of detecting transcripts of single class I genes in the MHC of C57BL/10 mice or sets of allelic class I genes at the same genetic locus in MHC disparate mouse strains. Using these probes, it is possible to determine the relative abundance of specific class I gene transcripts in a wide variety of cell and tissue types from inbred or MHC disparate mice. Examples of the use of these probes to detect different class I gene transcripts in cloned murine T cells, T cells transformed with Radiation Leukemia Virus, chemically induced thymoma cell lines and embryonic tissues are described. The results of these experiments are discussed in the light of possible roles of class I antigens in tumorigenesis or in early development.
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PMID:Analysis of major histocompatibility complex class I gene transcription using oligonucleotide probes. 350 10

Radiation-induced leukemia/lymphomas were induced in C57BL mice using four weekly acute 60Co fractionated irradiation exposures (to 188 cGy, or graded doses of low dose rate (LDR) Cf-252 irradiation given in fractionated exposure sessions at four weekly intervals. The acute 60Co radiation produced 84% thymic lymphomas with a median survival time (MST) of 162 days for mice developing tumors. Mice were exposed to Cf-252 n + gamma radiation in graded doses of 50, 62.5, 80, 112, and 188 cGy per week repeated 4X. Mice exposed to Cf-252 radiation developed thymic lymphomas on a much delayed time schedule. Mice irradiated at 50-80 cGy Cf-252 were killed after the 60Co induced thymoma mice had died to detect tumors. At Cf-252 doses of 112 or 188 rads 79 or 70% of mice, respectively, developed thymic lymphomas and had similar survival times which gave an estimated leukemogenesis RBEn of approximately 1.0-2.0. These studies show that for Cf-252 n + gamma radiation, compared to 60Co for leukemogenic efficiency, had a much longer latent period, and had a low RBE (1.0-2.0) at the large doses per fraction used in these studies. Under the experimental fractionated conditions tested, Cf-252 neutrons were leukemogenic, but only slightly more so than fractionated 60Co.
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PMID:Cf-252 leukemogenesis in the C57BL mouse. 380 18

Authors used a mouse lymphoma line--originated from a spontaneous AKR lymphoma--for serial transplantation into AKR mice. The homogenizate of the thymoma was always transplanted i.p. into the same mouse strain. When the cells taken from leukemic AKR mice were transplanted into adult C3H/He mice, these did not cause leukemia in the recipients. However, it turned out that the lymphoma cells were able to proliferate in the F3 hybrids of AKR male mouse crossed with C3H/He female. The question then arose, whether the donor cells originated from the AKR mouse grew and caused the lymphoma, or the transplanted cells would induce the cells of the recipient to develop lymphoma. On the basis of the results it was established that the AKR lymphoma cells themselves started developing in the recipients, when they were transplanted into hybrid mice and the cells of the recipient did not. The identification of the transplanted cells was done by the presence of the Rb [4.15] metacentric marker chromosome. These cells were found in the thymus, the lymph nodes and in the developing ascites of the hybrid mice. Two kinds of cell types were found in the lymph nodes, one of them contained the marker, while other did not. The spleen cells were free of the marker chromosome. These data suggest that the thymus manifestation of the AKR mouse lymphoma is heterogeneous--it consists at least of two major types of tumor cells. One of them has affinity to the thymus and the lymph nodes, while the other to the spleen and the lymph nodes too.
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PMID:Examinations concerning the development of lymphoma following transplantation i.p. of AKR mouse lymphoma cells into hybrid mice. 385 54

Galactosyltransferase activity (UDP-galactose:N-acetyl-D-glucosamine-D-galactosyltransferase) could be measured in thymus and sera from different strains of mice. Total thymic homogenates or thymocyte preparations obtained from thymoma carrying AKR/J mice exhibited higher enzyme activity compared to nonleukemic control mice. A similar difference was also noted in Swiss mouse thymus which develop thymic leukemia upon a single injection of 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboximide. Galactosidase, which was 25 times less active than galactosyltransferase, was not responsible for this difference. These observations were extended to an evaluation of the serum level of the enzyme as a potential tumor biomarker. A 3- to 4-fold increase in the activity of galactosyltransferase was detected in serum samples obtained from both leukemic mice models (AKR/J and Swiss) compared to the controls, whereas the sera from P388 tumor-bearing DBA/2 mice showed a statistically nonsignificant increase of only 20%. The data indicate that serum galactosyltransferase (that accepts the low-molecular-weight acceptor, N-acetyl-D-glucosamine) levels are elevated in the presence of thymic leukemia, and suggest the possibility of shedding of this enzyme from the tumor cells to the systemic circulation of the host. The implications, including the potential diagnostic significance of the results, are discussed.
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PMID:Elevated thymic and serum galactosyltransferase with low-molecular-weight acceptor activity in murine leukemia. 392 5


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