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

The c-abl locus is translocated from chromosome 9 to chromosome 22 in chronic myelogenous leukemia (CML), creating the Philadelphia chromosome (22q-, Ph1), one of the most consistent chromosomal abnormalities found in human hematologic malignancy. The K562 cell line is a human cell line originally derived from a patient with CML. We have isolated cloned human c-abl probes to analyze the organization and expression of abl genes in patients with CML and in K562 cells. With these probes, we confirm the amplification of abl genes in K562 cells. In addition, we demonstrate the presence of increased amounts of a novel RNA species hybridizing to a c-abl probe in K562 cells. This same large RNA species is present in addition to two normal transcripts in the leukemic cells of patients with CML. These results provide evidence that the c-abl locus is abnormally expressed in CML.
 ...
PMID:Increased expression of a novel c-abl-related RNA in K562 cells. 257 37

We report two cases of myeloproliferative syndromes in which the only karyotypic abnormality was an isochromosome of the long arm of chromosome 17. Because i(17q) is a nonrandom structural aberration found in nearly 12% of cases of Philadelphia (Ph)-positive chronic myelogenous leukemia (CML), we carried out a molecular analysis of the breakpoint cluster region (bcr) to verify the presence of genomic rearrangements characteristic of CML. The interest of the study was strengthened by the fact that i(17q) is frequently seen in CML and by recent reports showing that genomic changes of c-abl and bcr genes can be present even in the absence of a Ph chromosome. One of the two patients showed the presence of a rearranged fragment within the bcr, suggesting a Ph-positive CML diagnosis.
 ...
PMID:Molecular analysis of Philadelphia-negative myeloproliferative syndromes with i(17q). 259 64

Chronic myeloid leukemia (CML) is characterized by the Philadelphia chromosome which results from a reciprocal (9; 22) translocation, with the protooncogene c-abl moving from chromosome 9 to 22 and juxtaposed to the proximal bcr. Breakpoints on chromosome 22 are localized within 5.8 kb of the breakpoint cluster region (bcr). We have assessed the feasibility of using a 3'bcr probe for molecular diagnosis of CML. Thirty patients with Ph chromosome negative or positive CML were studied by Southern blot. A bcr rearrangement was seen to be present in all but one patient with Ph+CML. A case of Ph negative CML showed a bcr rearrangement. We conclude that this technique is efficient for molecular diagnosis of CML.
 ...
PMID:Molecular diagnosis of chronic myeloid leukemia using a 3'bcr probe. 261 68

The standard t(9;22)(q34;q11) found in Philadelphia (Ph) chromosome positive chronic myeloid leukemia (CML) involves a highly restricted (5.8 kb) chromosome 22 breakpoint cluster region (bcr), which results in the formation of a chimeric gene comprising exons from the 5' end of bcr and protooncogene c-abl coding sequences from chromosome 9. In a survey of 21 patients with hematologic and clinical features of CML we detected rearrangement of the chromosome 22 bcr by gene probe analysis in all cases, including 16 with a standard t(9;22), two with variant Ph translocations [t(10;22)(q26;q11);t(11;22)(p15;q11)], one with a complex Ph translocation [t(9;11;22)(q34;q13;q11)], one with a complex translocation and a masked Ph[t(9;14;22) (q34;q24;q11)], and one Ph-negative case with a t(1;9)(p32;q34). These observations further substantiate the suggestion that, despite karyotypic heterogeneity, a common underlying molecular lesion, the bcr-abl gene chimera, is involved in the disease pathogenesis of CML.
 ...
PMID:Chromosome 22 breakpoints in variant Philadelphia translocations and Philadelphia-negative chronic myeloid leukemia. 264 33

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.
 ...
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

bcr gene rearrangement and c-abl gene expression were analyzed in a patient with Philadelphia chromosome (Ph1)-positive hybrid acute leukemia with simultaneous proliferation of lymphoid and myeloid blasts. These data were compared with those from a patient with chronic myelogenous leukemia (CML) in mixed crisis. The leukemic cells of both patients showed immuno-phenotypic profiles such as non-T, non-B common ALL with some MPO-positive leukemic cells and rearranged JH genes. On analysis of molecular events associated with the Ph1 chromosome, the leukemic cells of a patient with CML in mixed crisis showed bcr rearrangement and an 8.5-kb bcr-abl chimeric mRNA, but those of a patient with Ph1-positive hybrid acute leukemia showed no 8.5-kb bcr-abl mRNA, as previously reported in a number of Ph1-positive acute lymphoblastic leukemia (ALL) cases. These results revealed that the molecular event found in Ph1-positive ALL is not only restricted to lymphoid lineage but may play an important role in the proliferation of the myeloid lineage.
 ...
PMID:bcr rearrangement and C-abl gene expression in Ph1-positive hybrid acute leukemia with simultaneous proliferation of lymphoid and myeloid blasts. 265 44

Chronic myelogenous leukemia (CML) is associated with the reciprocal translocation of a region of chromosome 22 called BCR with the c-abl gene of chromosome 9.5' coding sequences from the BCR gene are spliced in-frame to the second exon of the ABL gene to produce a CML-specific 8.5 kilobase message which encodes the BCR-ABL hybrid protein P210. To definitively identify and characterize the normal BCR gene product, sequences from BCR cDNA clones were used to reconstitute the coding portion of the normal message in retroviral and bacterial transcription vectors. The normal BCR gene product was demonstrated to be a phosphoprotein of 160 kilodaltons by in vitro translation and immunoprecipitation from lysates of NIH3T3 lines expressing BCR retroviruses. Whereas BCR-homologous RNA levels in these cell lines were increased 50 fold, BCR protein levels increased only 2 to 10 fold depending on the presence or absence of BCR-specific 5' and 3' untranslated regions. We observe a kinase activity associated with this protein but we do not observe morphological transformation of NIH3T3 cells as a result of its overproduction.
 ...
PMID:Structural characterization of the BCR gene product. 265 72

In a case of CML with a variant Philadelphia translocation (Ph1 or Ph) t(22;22) (q11;q13) in bone marrow cells and unstimulated peripheral blood cells, no cytogenetically detectable involvement of chromosome 9 was observed. Southern blot experiments using probes specific for bcr and c-sis however revealed rearrangement of the bcr, but not of PDGFB (c-sis) gene. Northern blot analysis of bone marrow RNA showed a very weak signal with the c-sis probe, while in a lymph-node biopsy PDGFB m-RNA could not be detected. Chromosomal in situ hybridization gave evidence for translocation of c-abl from chromosome 9 to Ph and of PDGFB from chromosome 22 to chromosome 9, as the result of a threefold translocation t(9;22;22).
 ...
PMID:Translocation of c-abl oncogene and PDGFB (c-sis) gene in a case of CML with 46,XY, t(22;22). 266 Sep 25

Structural abnormalities of the c-abl proto-oncogene are found in hematopoietic cells of more than 90 percent of individuals with chronic myelogenous leukemia. Therefore c-abl may be important in normal as well as malignant hematopoiesis. Normal human hematopoietic progenitor cells were exposed to three different c-abl sense or antisense oligodeoxynucleotides, and the effects on myeloid and erythroid colony formation were examined. The c-abl antisense oligodeoxynucleotides inhibited myeloid, but not erythroid, colony formation. The c-abl sense oligodeoxynucleotides and bcr sense and antisense oligodeoxynucleotides were not inhibitory in this assay. These data show that c-abl is critical in normal myelopoiesis and may explain the relatively selective expansion of leukocytes in patients with chronic myelogenous leukemia.
 ...
PMID:Lineage-specific requirement of c-abl function in normal hematopoiesis. 267 39

Five to ten percent of the Ph-positive cases of chronic myelogenous leukemia (CML), termed variant translocations, involve at least one chromosome in addition to 9 and 22 in the abnormality. The involvement of chromosome 9 band q34, where the c-abl oncogene has been localized, is not always cytogenetically detectable in so called variant translocations due to complex rearrangements. We present two cases having the most frequently involved chromosomes (#3 and #17) in such translocations. In one case, both chromosome 9's were cytogenetically normal while in the other, band 9q34 was so called 'masked' or 'hidden'. After molecular evaluation using in situ hybridization and Southern blotting techniques, the involvement of the altered bcr/abl gene was demonstrated and the cytogenetic analysis was revised. Utilization of molecular probes in the evaluation of such cases should become a routine diagnostic procedure in detecting the exchange of bcr and c-abl sequences.
 ...
PMID:Molecular characterization of variant translocations in chronic myelogenous leukemia. 267 57


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>