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Query: UMLS:C0596978 (Leukemia)
 15,069 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seven patients with Philadelphia (Ph) chromosome positive essential thrombocythemia (ET) were investigated for the presence of a rearrangement within the major breakpoint cluster region (M-bcr) using the Southern blot technique and, in six cases, for the presence of the hybrid bcr-abl mRNA using the polymerase chain reaction (PCR). The molecular studies showed rearrangement of M-bcr in all cases; there was evidence of the b2a2 mRNA junction in one case and of b3a2 junction in five cases. These findings are identical to what might have been expected in Ph-positive chronic myeloid leukemia. These features may explain the poor prognosis of Ph-positive ET in comparison with cytogenetically normal cases. Conversely, the differences in clinical presentation may be due to other genetic changes.
Leukemia 1989 Aug
PMID:Molecular analysis of Philadelphia positive essential thrombocythemia. 274 91

Leukemic cell DNA from patients with Philadelphia chromosome positive chronic granulocytic leukemia in the United Kingdom, Taiwan, and South Africa and of diverse ethnic origins all have identifiable molecular rearrangements of the breakpoint cluster region on chromosome 22 band q11 when screened with an appropriate DNA probe. This result reinforces the highly conserved nature of the molecular lesion in chronic granulocytic leukemia and its suitability as a diagnostic marker for the disease. Since the assay can be performed by sample referral on relatively small numbers of nondividing frozen or dead cells, it is ideally suited for large scale epidemiological and clinical studies, particularly in developing countries where karyotyping services are not readily available.
Leukemia 1987 Jun
PMID:Molecular lesion in chronic granulocytic leukemia is highly conserved despite ethnic and geographical variation. 282 24

We surveyed DNAs from patients with various hematological malignancies by Southern blot hybridization to analyze bcr rearrangements, and detected a new restriction fragment length polymorphism (RFLP) of the breakpoint cluster region at a BamHI site in three patients. By using a 1.2-kb HindIII-BglII 3' bcr probe, unusual BamHI restriction enzyme fragments (1.9 kb and 1.4 kb) were detected from the DNAs of three patients with hematological malignancies. DNAs from cultured fibroblasts derived from the skin of a patient, as well as from peripheral leukocytes of the father of a patient and the mother of another patient, showed identical 1.9- and 1.4-kb additional bands, besides a 3.3-kb germline band, establishing that polymorphism, rather than gene arrangement, was responsible for these additional restriction enzyme fragments. However, RFLP was not detected in the DNAs of 40 normal unrelated individuals.
Leukemia 1988 Oct
PMID:Restriction fragment length polymorphism of bcr in Japanese patients with hematological malignancies. 290 58

Detection of rearrangement of the breakpoint cluster region (bcr) of chromosome 22 by Southern blot analysis can be used for the routine diagnosis of CML. Restriction fragment length polymorphisms (RFLPs) in the bcr can potentially be confused with translocation since both alter the size of DNA fragments obtained. By digesting DNA with the restriction enzyme BamHl and analyzing with probes commonly used for identifying rearrangement of the bcr, we have observed a RFLP within the bcr. For one CML patient studied in detail, the presence of the polymorphism was confirmed by comparing the results of analyses of granulocytes and a T cell-enriched population. The same polymorphism was detected in three additional CML patients and a patient with thrombocytosis. For the diagnosis of CML, verification of rearrangement with multiple probes and/or restriction enzyme combinations is necessary to rule out false positives, as well as to reduce the chance of false negatives due to co-migration of DNA fragments.
Leukemia 1988 Nov
PMID:A rare restriction enzyme site polymorphism in the breakpoint cluster region (bcr) of chromosome 22. 290 73

We report here the case of a patient with refractory anemia with excess of blasts (RAEB) which evolved into RAEB in transformation. The standard Philadelphia (Ph) chromosome was found by cytogenetic study at diagnosis and during evolution. Southern blot analysis showed breakpoint cluster region (bcr) rearrangement as observed in chronic myelogenous leukemia (CML).
Leukemia 1989 Mar
PMID:Cytogenetic and molecular studies of the Philadelphia translocation t(9;22) observed in a patient with myelodysplastic syndrome. 291 60

We report the clinical evaluation of an improved DNA probe assay for the characteristic genetic marker of human CML, observed by cytogenetics and designated the Philadelphia chromosome (Ph1). The Ph1 chromosome results from the fusion of c-abl proto-oncogene sequences from chromosome 9 to phl gene sequence on chromosome 22. (The phl gene is often referred to as bcr. However, for clarity we prefer to reserve the designation "bcr" for the region within the phl gene in which translocation breakpoints have been found to occur. We also find it useful to distinguish between two such regions in phl, bcr-210 and bcr-190, named after the 210- and 190-kDa phl/abl fusion proteins resulting from translocations with breakpoints in the respective regions. We refer to the corresponding chromosomal translocations as Ph1(bcr-210) and Ph1(bcr-190).) DNA, extracted from peripheral blood (PB) or bone marrow (BM) and digested with restriction endonuclease BglII, is hybridized with a probe (phl/bcr-3) spanning a breakpoint cluster region within phl. Rearrangements are revealed by the presence of one or two novel junction fragments. Clinical specimens from leukemic patients with active disease were compared by cytogenetic and DNA probe analysis at seven centers in the United States and Europe. The probe assay identified the phl rearrangement in 190 of 191 cases of Ph1-positive CML, as well as in 12 of 27 clinically diagnosed CML specimens lacking a typical Ph1 chromosome. DNA rearrangements also were seen in two of six cases of Ph1-positive ALL. No false positive results were obtained among 93 non-leukemic controls. Mixing experiments showed that the DNA probe assay can detect as few as 1% leukemic cells in a specimen. A preliminary study of CML patients in remission after allogeneic BM transplantation revealed a small fraction of residual Ph1-positive leukemic cells in a significant number of such patients.
Leukemia 1988 Oct
PMID:Clinical evaluation of a DNA probe assay for the Philadelphia (Ph1) translocation in chronic myelogenous leukemia. 305 Feb 93

Molecular rearrangements of Ph1 chromosome, the hallmark of CML, are clustered in a 5.8-kb DNA segment, the so-called breakpoint cluster region (bcr) of the phl gene that is localized to chromosome 22q11. In Ph1-positive (Ph1+) ALLs, the rearrangements have been shown to involve either the 5.8-kb bcr (called bcr+) or a region upstream of bcr in the 5' end of the phl gene (bcr-). To gain insight into the rearrangements occurring in Ph1+ acute leukemias, a 64-kb DNA fragment from the 5' end of phl was analyzed in order to generate molecular probes covering 40 kb of the phl gene first intron. A panel of seven cases of bcr-Ph1+ acute leukemia (three nonlymphocytic and four lymphocytic) was investigated with these intron 1-derived probes. Strikingly, in six of the seven leukemias, the breakpoints were located in a 10.8-kb DNA segment, defining a new bcr which appears to be specific for Ph1+ acute leukemias. By analogy with the CML bcr region located in the 3' part of the phl gene, we propose to designate this 10.8-kb fragment bcr2.
Leukemia 1988 Oct
PMID:Molecular cloning of a 5' segment of the genomic phl gene defines a new breakpoint cluster region (bcr2) in Philadelphia-positive acute leukemias. 317 40

Rearrangement of the breakpoint cluster region (bcr) was demonstrated by Southern blot analysis in the DNA in each of 68 patients with Ph chromosome-positive CML and in 3 of 7 patients with apparent Ph chromosome-negative CML. In contrast, no bcr rearrangement could be found in DNA from 17 normal individuals and 28 patients with various hematologic disorders other than CML or ALL. An analysis of the location of the breakpoints within the bcr indicated that 3' breakpoints were significantly more common in patients in blast crisis or accelerated phase disease compared to those with chronic phase disease. Patients with chronic phase disease and 3' breakpoints had shorter average disease duration than that for chronic phase patients with 5' breakpoints, although the difference between these two groups of patients was not statistically significant. For patients who had progressed to accelerated disease or blast crisis, a statistically significant difference in chronic phase disease duration could be demonstrated between 11 patients with 3' breakpoints (average chronic phase 30.2 months) and 15 patients with 5' breakpoints (average chronic phase 50.6 months). For 8 patients studied in both chronic phase and accelerated or blast crisis, the location of the breakpoint did not change. We suggest that the bcr-abl fusion protein associated with a 3' breakpoint could result in more rapid progression to acute disease, and this may account for differences in the relative frequency of 3' and 5' breakpoints at different disease stages. Although more studies are required, identifying CML patients with a higher propensity for early blast transformation may eventually prove to be of some clinical value.
Leukemia 1988 Oct
PMID:The location of breakpoints within the breakpoint cluster region (bcr) of chromosome 22 in chronic myeloid leukemia. 317 41

Basophils were isolated from the peripheral blood of two patients with Philadelphia positive-chronic myeloid leukemia using monoclonal antibody Bsp-1 and fluorescence activated cell sorting. DNA blot analyses demonstrated rearrangement of the breakpoint cluster region gene in the isolated basophils, which suggests their leukemic origin. Isolated T cells from these patients that were cultured for 14 days in the presence of interleukin-2 lacked rearrangement of the breakpoint cluster region gene and are therefore unlikely to be derived from the chronic myeloid leukemia clone.
Leukemia 1988 Mar
PMID:Basophils exhibit rearrangement of the bcr gene in Philadelphia chromosome-positive chronic myeloid leukemia. 325 49

Analysis at the DNA and RNA level revealed a mature genetic marker profile in a case of T type blast crisis of chronic myelocytic leukemia. T cell receptor beta chain gene rearrangement as well as T cell receptor alpha mRNA transcription was demonstrated in blasts of the malignant clone. Corresponding findings were obtained from immunological phenotyping. Blasts were found to be CD7+, CD1+, CD3+, CD4+, CD8+, and TdT- and classified as common/mature thymocytes. The presence of the breakpoint cluster region gene on chromosome 22 excluded the possibility of a second neoplastic process.
Leukemia 1988 Mar
PMID:T cell receptor alpha mRNA transcription in T-lymphoblastic transformation of chronic myelocytic leukemia. 325 50


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