Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The polymerase chain reaction (PCR) allows the detection of minimal amounts of nucleic sequences and has been successfully used to test for the chronic myeloid leukemia-specific bcr/abl transcripts. We studied blood samples from 17 patients who had undergone allogeneic bone marrow transplantation for CML, using a modified polymerase chain reaction-based assay for the detection of leukemic mRNA. This nested PCR technique was found to be highly sensitive, detecting the chimeric bcr/abl transcript in 16 of 17 patients including several long-term survivors. Cytogenetic techniques failed to detect Ph mitoses. The clinical significance of the persisting bcr/abl transcript for long periods following BMT is poorly understood and remains to be elucidated by further studies.
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PMID:Frequent detection of minimal residual disease by use of the polymerase chain reaction in long-term survivors after bone marrow transplantation for chronic myeloid leukemia. 240 20

In tumor cells from virtually all patients with chronic myelogenous leukemia, the Philadelphia chromosome, a fusion of chromosomes 9 and 22, directs the synthesis of the P210bcr/abl protein. The protein-tyrosine kinase activity and hybrid structure of P210bcr/abl are similar to the oncogene product of the Abelson murine leukemia virus, P160gag/v-abl, which induces acute lymphomas. To determine whether P210bcr/abl can induce chronic myelogenous leukemia, murine bone marrow was infected with a retrovirus encoding P210bcr/abl and transplanted into irradiated syngeneic recipients. Transplant recipients developed several hematologic malignancies; prominent among them was a myeloproliferative syndrome closely resembling the chronic phase of human chronic myelogenous leukemia. Tumor tissue from diseased mice harbored the provirus encoding P210bcr/abl. These results demonstrate that P210bcr/abl expression can induce chronic myelogenous leukemia. Retrovirus-mediated expression of the protein provides a murine model system for further analysis of the disease.
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PMID:Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. 240 2

Antibodies against phosphotyrosine are a powerful tool with which to identify proteins phosphorylated on tyrosine residues, such as viral oncogene-encoded transforming proteins and their cellular protein substrates. Probed on human leukemia cell lines, phosphotyrosine antibodies recognized a 210,000-molecular-weight protein (p210) in K562 cells, a cell line derived from a Philadelphia (Ph)'-positive chronic myelogenous leukemia (CML), but recognized no protein in control Ph'-negative non-CML leukemia cells. The p210 protein was also recognized by antisera against v-abl-encoded polypeptides and displayed kinase activity, phosphorylating itself on tyrosine, in an immunocomplex kinase assay. These data are consistent with reported findings of the expression of a recombined bcr-abl gene in Ph'-positive CML cells, leading to the synthesis of an altered p210c-abl protein endowed with tyrosine kinase activity. Phosphotyrosine antibodies also detected the expression of the p210c-abl protein in fresh bone marrow cells harvested from CML patients in blast crisis. Besides the p210c-abl protein kinase, phosphotyrosine antibodies recognized other proteins with molecular weights of 110,000, 68,000, and 36,000 (p110, p68, and p36) in K562 cells. When [gamma-32P]ATP was added to nonionic detergent-extracted cells, these proteins became phosphorylated on tyrosine, as confirmed by phosphoamino acid analysis. A comparison with fibroblasts transformed by the v-abl, v-src, and v-fps oncogenes suggested the identity of the p36 protein with the common 36-kilodalton protein substrate of viral oncogene-encoded tyrosine kinases. Enhanced tyrosine phosphorylation of cellular proteins is thus a feature shared by cells transformed by v-abl and cells expressing a rearranged bcr-abl gene.
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PMID:Phosphotyrosine antibodies identify the p210c-abl tyrosine kinase and proteins phosphorylated on tyrosine in human chronic myelogenous leukemia cells. 243 Dec 86

An altered c-abl gene product (P210bcr-abl) possessing associated tyrosine protein kinase activity was recently been reported in several blast chronic myelogenous leukemia (CML) cell lines. We have examined different morphological types of leukocytes directly obtained from patients at the blast crisis stage of CML for expression of P210bcr-abl tyrosine protein kinase activity. Phosphorylation of P210bcr-abl in an immune complex kinase assay using an anti-v-abl peptide serum was observed in blast cells from four Philadelphia chromosome (Ph1)-positive CML patients in blast crisis. P210bcr-abl protein kinase activity was detected regardless of whether the blast cells were of myeloid, lymphoid, or undifferentiated morphology. P210bcr-abl protein kinase activity was not detected in immune complexes either from leukocytes of four Ph1-negative CML patients in blast crisis, of five acute myelogenous leukemia patients, or in the promyelocytic cell line HL-60. Mature myeloid cells are associated with an inhibitory factor for not only P210bcr-abl protein kinase activity, but also protein kinases in general. Therefore, analyses of Ph1-positive benign phase CML myeloid cells, the majority of which are well differentiated, could not be successfully performed. The inhibition of P210bcr-abl protein kinase activity is not a specific property of mature cells from CML patients since granulocytes from a normal volunteer also demonstrated a similar effect. However, extracts of Ph1-positive cultured B-lymphocytes from a patient in benign phase demonstrated active P210bcr-abl protein indicating that the P210bcr-abl protein is expressed in an enzymatically active form in the earlier phases of CML. In addition to the previously reported P210 and P190 abl-related proteins, a novel Mr 53,000 protein was found to undergo phosphorylation at serine and tyrosine in immune complex kinase assays of two blast crisis CML cell lines (K562 and EM2) and in samples from blast crisis patients in which P210bcr-abl was detected. Peptide mapping by the Cleveland technique suggested that Mr 53,000 protein is unrelated to P210bcr-abl. Immune complex kinase assays of K562 cells with an anti-src serum (GD-11) yielded active c-src kinase and a Mr 50,000 phosphorylated protein, both of which were resistant to alkaline hydrolysis. Peptide mapping suggested that Mr 53,000 protein is related to Mr 50,000 protein which is precipitated with P210bcr-abl as an Mr 300,000 protein complex.
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PMID:Analysis of P210bcr-abl tyrosine protein kinase activity in various subtypes of Philadelphia chromosome-positive cells from chronic myelogenous leukemia patients. 243 23

The v-abl oncogene of the Abelson murine leukemia virus (A-MuLV) is known to efficiently transform NIH/3T3 fibroblasts in vitro and to cause an acute lymphosarcoma in susceptible murine hosts. The role of its relative, the bcr/abl gene product, in the etiology of human chronic myelogenous leukemia (CML) remains speculative. To assess the transforming properties of the bcr/abl gene product, complementary DNA clones encoding the CML-specific P210 bcr/abl protein were expressed in NIH/3T3 fibroblasts. In contrast to the v-abl oncogene product P160, the P210 bcr/abl gene product did not transform NIH/3T3 cells. Cell lines were isolated that expressed high levels of the P210 bcr/abl protein but were morphologically normal. During the course of these experiments, a transforming recombinant of bcr/abl was isolated which fuses gag determinants derived from helper virus to the NH2-terminus of the bcr/abl protein. This suggests that a property of viral gag sequences, probably myristylation-dependent membrane localization, must be provided to bcr/abl for it to transform fibroblasts.
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PMID:The CML-specific P210 bcr/abl protein, unlike v-abl, does not transform NIH/3T3 fibroblasts. 244 Jan 7

The Philadelphia (Ph1) chromosome in chronic myelogenous leukemia (CML) involves reciprocal translocation of the bcr gene and the c-abl oncogene. The fused bcr/abl gene is transcribed into two types of chimeric mRNA. By means of a combined method of S1 nuclease protection and polymerase chain reaction, we amplified sequences representative of the chimeric bcr/abl transcripts. Only 5 micrograms of total cellular RNA is needed and the chimeric bcr/abl message can be detected at a dilution of 1:100,000. We also detected residual chimeric bcr/abl transcripts in the remission samples from two Ph1-positive CML patients. This technique has the potential to identify a subpopulation of Ph1-positive CML patients in remission who are at high risk of relapse.
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PMID:Detection of minimal residual bcr/abl transcripts by a modified polymerase chain reaction. 245 51

We established a B lymphocyte line from bone marrow cultures of a patient with Philadelphia chromosome (Ph1) positive chronic myelogenous leukemia. The cell line (MB) is positive for Ph1 and has the phenotype of mature B lymphocytes transformed by the Epstein-Barr virus (EBV). When DNA was isolated and hybridized to specific cDNA probes, a rearranged immunoglobulin gene and EBV-sequences were detected. On Western blots of cell extracts, the novel fusion protein (P 210) was demonstrated with antisera against bcr and v-abl proteins. These results confirm the concept that B lymphocytes in CML can be involved in the malignant clone and demonstrate that these B cells express the fusion protein.
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PMID:A Ph1 chromosome positive B cell line expresses the fusion protein P 210. 249 56

An altered c-abl protein (P210) bearing increased tyrosine kinase activity represents the product of the hybrid bcr/c-abl gene arising as a consequence of the Philadelphia (Ph1) chromosome translocation, the consistent cytogenetic abnormality of chronic myelogenous leukemia (CML). Although the chronic phase of this disease is substantially characterized by a marked proliferation of myeloid cells, the Ph1 translocation occurs in an early multipotent stem cell, giving rise to both myeloid and lymphoid cell lineages. Here we show that P210 bcr/abl protein expression varies greatly in different Ph1 chromosome positive B-lymphoid cell lines obtained from Epstein-Barr virus-transformed lymphocytes of a CML patient in the chronic phase. In addition Ph1 positive and Ph1 negative lymphoid cell lines obtained from the same patient were tested for a number of biological properties including the immunophenotype, the capacity to grow in soft agar and possible tumorigenicity in nude mice. No differences were found.
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PMID:Expression of the hybrid P210 bcr/abl protein in Philadelphia chromosome positive B-lymphoid cell lines. 251 Oct 93

The occasional finding of cells positive for the Philadelphia (Ph) chromosome months or years after bone-marrow transplantation for chronic myeloid leukaemia raises the possibility that the Ph-positive clone may never be eradicated. The polymerase chain reaction with probes able to detect the transcript of the bcr/abl hybrid gene at very low levels was used to study marrow cells from seven patients in continuing haematological and cytogenetic remission 5-7 years after allogeneic bone-marrow transplantation for chronic myeloid leukaemia. No evidence of the leukaemic mRNA was found. Thus, it seems that all leukaemic cells were eradicated in these patients and that they are truly cured.
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PMID:Polymerase chain reaction for detection of residual leukaemia. 256 20

We investigated the practical value of antisense RNA/mRNA in situ hybridization for the detection of low level expression of the c-abl oncogene in non-Hodgkin lymphomas. This is of clinical relevance, since we recently showed that low level expression of this proto-oncogene mainly occurs in advanced stage disease of non-Hodgkin lymphomas and in cases of chronic lymphocytic leukemia with progressive course of the disease (Greil R, Gattringer C, Fasching B, Cleveland J, Thaler J, Radaskiewicz T, Gastl G, Huber C, Rapp U, Huber H: Int J Cancer 42:529 1988). When numerous technical parameters were tested for the adaptation of the method, fixation with 4% paraformaldehyde, gelatin coating of the slides, the time concentration product of proteinase K, and the kind of labeling had the greatest impact on results and successful performance of the technique. When the optimized method was applied to the v-abl-transformed NIH 3T3-, the K 562 CML blast cell line and to nine cases of lowly malignant non-Hodgkin lymphomas it semiquantitatively discriminated the varying amounts of v-abl, bcr/c-abl and c-abl mRNA expressed within these cells. Parallel analysis with Northern blotting confirmed the specificity of the method and pointed to a very high sensitivity, including the capacity to detect only few c-abl mRNA molecules/cell. An essential advantage of in situ hybridization was the detection of inhomogeneous expression of the c-abl mRNA within subpopulations of the malignant clone. In addition, this technique might be of particular importance when a gene is only weakly expressed on a small fraction of cells which might easily escape the detection by Northern blotting. Immunocytochemical investigation suggested parallel expression of the oncoprotein in six of seven c-abl mRNA positive cases as well as high specificity and sensitivity for the polyclonal and to a lesser extent for one monoclonal antibody. However, because of the high potential of cross-reactivity of anti-oncoprotein antibodies, parallel investigations on the mRNA level should be performed particularly when new anti-oncoprotein antibodies are applied. Our results demonstrate that this can be performed using in situ hybridization, even when the number of mRNA targets is very low.
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PMID:In situ hybridization for the detection of low copy numbers of c-abl oncogene mRNA in lymphoma cells: technical approach and comparison with results with anti-oncoprotein antibodies. 265 1


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