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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Structural rearrangements of specific cellular sequences (c-onc genes) homologous to acute transforming retrovirus oncogenes (v-onc genes) have been recently described in various malignancies. Here we show that human cellular sequences (c-abl) homologous to the transforming sequences of the mouse Abelson leukemia virus (v-abl) are amplified some 4- to 8-fold in K-562, a Philadelphia chromosome-positive cell line derived from a patient with chronic myelogenous leukemia in blast crisis. Restriction analysis of K-562 and other human DNA samples reveals a significant rearrangements of the c-abl sequences in this cell line. In addition, investigation of v-abl-related cytoplasmic RNA reveals relatively high levels of these sequences in K-562 compared to other normal and leukemia cells. We have also observed that lambda light chain constant region immunoglobulin genes are amplified in K-562, whereas kappa light chain sequences exhibit no amplification. These results are discussed within the context of the possibility that these Philadelphia chromosome-positive cells exhibit a reciprocal translocation involving chromosome 9 (containing c-abl) and chromosome 22 (containing the lambda light chain genes).
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PMID:Rearrangement and amplification of c-abl sequences in the human chronic myelogenous leukemia cell line K-562. 630 52

The mouse c-abl gene, part of the sequence of which was captured in Moloney murine leukemia virus to generate the transforming gene (v-abl) of the Abelson murine leukemia virus, has been isolated and characterized. The c-abl locus spans 40 kb in the mouse genome with the v-abl homologies distributed in no less than ten clusters along 25 kb of the cloned DNA. Partial sequence of the v-abl homologous regions indicates that v-abl derived from c-abl mainly by splicing of multiple exons of the c-abl gene. The c-abl sequences can be subdivided into two regions: a tyrosine kinase coding sequence distributed among eight small clusters on the 5' end of the gene and a C-terminal portion consisting of one small and one large cluster, which are needed neither for the tyrosine kinase activity nor for the transforming ability of v-abl. Apparent exon/intron boundaries in the homologous kinase-coding regions of c-abl and c-src are at different locations.
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PMID:The mouse c-abl locus: molecular cloning and characterization. 631 18

Three types of tumors termed plasmacytomas (ABPC's), lymphosarcomas (ABLS's), and plasmacytoid lymphosarcomas (ABPL's) arise in BALB/c mice treated with pristane and Abelson murine leukemia virus (A-MuLV). While most ABPC's and BLS's contain integrated A-MuLV proviral genome and synthesize the v-abl RNA, most ABPL's do not. The ABPL tumors were examined for the expression of other oncogenes that may be associated with their transformed state, in the absence of transforming virus. These tumors expressed abundant c-myb RNA of unusually large size and showed DNA rearrangements of the c-myb locus.
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PMID:DNA rearrangement and altered RNA expression of the c-myb oncogene in mouse plasmacytoid lymphosarcomas. 668 62

The transforming genes of oncogenic retroviruses are homologous to a group of evolutionary conserved cellular onc genes. The human cellular homologue (c-abl) of the transforming sequence of Abelson murine leukaemia virus (A-MuL V) was recently shown to be located on chromosome 9. The long arm of this chromosome is involved in a specific translocation with chromosome 22, the Philadelphia translocation (Ph1), t(9; 22) (q34, q11), which occurs in patients with chronic myelocytic leukaemia (CML)3-5. Here we investigate whether the c-abl gene is included in this translocation. Using c-abl and v-abl hybridization probes on blots of somatic cell hybrids, positive hybridization is found when the 22q- (the Philadelphia chromosome), and not the 9q+ derivative of the translocation, is present in the cell hybrids. From this we conclude that in CML, c-abl sequences are translocated from chromosome 9 to chromosome 22q-. This finding is a direct demonstration of a reciprocal exchange between the two chromosomes and suggests a role for the c-abl gene in the generation of CML.
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PMID:A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia. 696 Feb 56

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.
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PMID:Transforming gene of a human leukaemia cell is unrelated to the expressed tumour virus related gene of the cell. 712 5

Herbimycin A, a benzoquinonoid anasamycin antibiotic, preferentially inhibited the in vitro growth of Ph1-positive leukemia cell lines. On the other hand, genistein, which was developed as an inhibitor of receptor-type tyrosine kinase, and other protein kinase inhibitors showed no selective inhibition of Ph1-positive leukemia cell growth. Herbimycin A also displayed an abrogative effect on the transformation of murine hematopoietic cells by transfection with a bcr/abl oncoprotein-expressing retroviral vector. The antitumor action of herbimycin A on Ph1-positive leukemia cells is related to an inhibition of activity of bcr/abl protein tyrosine kinase and a subsequent reduction of the constitutive phosphotyrosyl proteins, however, the antibiotic has no effect on the expression of bcr/abl mRNA and oncoprotein. Therefore, herbimycin A may provide an important insight into the oncogenic action of bcr/abl oncoprotein and the future development of oncoprotein-targeted therapeutic agents.
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PMID:Effect of herbimycin A, an inhibitor of tyrosine kinase, on protein tyrosine kinase activity and phosphotyrosyl proteins of Ph1-positive leukemia cells. 751 Nov 93

We describe a patient with acute nonlymphocytic leukaemia (ANLL) derived from myelodysplastic syndrome in whom the Philadelphia chromosome (Ph1) first emerged at the late stage of ANLL transformation. Cytogenetically, the Ph1 chromosome was not detected until the late stage of ANLL transformation, 14 months after the transformation following a 3-month history of refractory anaemia with excess of blasts. The cells with and without the Ph1 chromosome had a common abnormal chromosome, t(3;3) (q21;q26). The reverse transcription-polymerase chain reaction analysis showed no bcr/abl message at diagnosis. However, the mRNA encoding P210bcr/abl was detected in the early stage of ANLL transformation. Furthermore, the mRNAs encoding both P210bcr/abl and P190bcr/abl were detected in the late stage of ANLL transformation when the Ph1 chromosome was detected by cytogenetic analysis. These evidences support a multistep pathogenesis of leukaemias, and the products of bcr/abl fusion gene may influence the course of disease.
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PMID:Late-appearing Philadelphia chromosome in a patient with acute nonlymphocytic leukaemia derived from myelodysplastic syndrome: detection of P210- and P190-type bcr/abl fusion gene transcripts at the leukaemic stage. 752 18

The aims of this study were to investigate the role of cytokines (tumour necrosis factor alpha (TNF alpha), interferon gamma (IFN gamma) and interleukin-2 (IL-2) in augmenting graft-versus-leukaemia (GVL). We have investigated the effector cells involved in GVL, by studying the role of these cells in purging of the cell line K562 in short-term bone marrow cultures. The effect of the addition in vitro of rGCSF was also studied. Monitoring of purging was achieved by cytotoxicity assays, DNA analysis and the use of the polymerase chain reaction for the detection of bcr/abl transcripts in the Philadelphia positive (Ph+) K562 cell line. Supernatants from IL-2-treated and non-treated bone marrow were tested for cytokine production (TNF alpha and IFN gamma). The results have shown that the main cytotoxic effector cells in the bone marrow generated by IL-2 have the CD56+ CD8+ phenotype. Overnight incubation of bone marrow was sufficient to generate cytotoxic cells as measured by Chromium51 (Cr51) release assays. Measurable levels of TNF alpha but not IFN gamma were also detected in supernatants. Addition of TNF alpha and IFN gamma to the IL-2 in the bone marrow cultures augmented the cytotoxicity but tended to inhibit progenitor cell growth as measured by granulocyte-macrophage colony-forming unit (GM-CFU) and erythroid blast-forming unit (BFU-e) assays. An estimate of the purging of the marrow could also be achieved by DNA analysis of K562 DNA in bone marrow. The bcr/abl transcript could still be detected by PCR analysis in marrow containing 1% K562 and treated with IL-2 for 24 h, but by 6 days of incubation the bcr/abl transcript was weak or undectable. The results suggest that although reduction in the proportion of leukaemia in contaminated marrow can be detected after incubation with IL-2 for 24 h, complete elimination of minimal residual disease requires longer incubation times.
Leukemia 1995 Mar
PMID:Cytokine treatment of human bone marrow activates anti-leukaemia effector cells: monitoring of purging by polymerase chain reaction and DNA analysis. 753 66

DNA is a very stable molecule and fixation as well as routine histological processing does not destroy its molecular structure. Hence the possibility exists to use this material for molecular genetic analyses. The polymerase chain reaction (PCR) opens the chance to amplify DNA to huge amounts from pathological paraffin and plastic blocks and to use this DNA for further examinations, such as detection of mutations or translocations in malignant tumors, e.g. t(14;18) in follicular lymphomas, bcr/abl in chronic myeloic leukemia, t(11;22) in Ewing sarcomas or of the ras-gene in colon cancer, overexpression of tumor related mRNA, e.g. mdr1-mRNA of the multidrug associated P-Glycoprotein, or detection of foreign DNA from viruses or bacteriae, as well as analysis of hereditary diseases. PCR in its various forms (conventional PCR, PCR with direct sequencing, reverse transcriptase (RT)-PCR, nested primer PCR, quantitative RT-PCR, inverse PCR, degenerated primer (DOP) PCR, in situ PCR, in situ RT-PCR etc.) has proven to supplement routine diagnostic work in many occasions, however, it has to be emphasized that up to now there exists no example for a complete replacement of histological or immunhistological examination by PCR. As consequence, histology remains the first and most important step towards a relevant diagnosis supplemented e.g. by PCR and other techniques of molecular biology.
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PMID:[Polymerase chain reaction in diagnostic pathology]. 753 75

Deregulated expression of v-abl and BCR/abl genes has been associated with myeloproliferative syndromes and myelodysplasia, both of which can progress to acute leukemia. These studies identify the localization of the oncogenic form of the abl gene product encoded by the Abelson murine leukemia virus in the nuclei of myeloid cells and the association of the v-Abl protein with the transcriptional regulator cyclic AMP response element-binding protein (CREB). We have mapped the specific domains within each of the proteins responsible for this interaction. We have shown that complex formation is a prerequisite for transcriptional potentiation of CREB. Transient overexpression of the homologous cellular protein c-Abl also results in the activation of promoters containing an intact CRE. These observations identify a novel function for v-Abl, that of a transcriptional activator that physically interacts with a transcription factor.
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PMID:Nuclear localization of v-Abl leads to complex formation with cyclic AMP response element (CRE)-binding protein and transactivation through CRE motifs. 756 61


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