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

Philadelphia (Ph) chromosome-positive chronic myelogenous leukaemia (CML) was studied in a subject heterozygous for the X chromosome-linked alloenzyme system of glucose-6-phosphate dehydrogenase (G6PD). Determination of G6PD mosaicism showed homogeneous expression in granulocytes, erythrocytes and platelets. Cytogenetic studies showed the typical Ph translocation in all metaphases from bone marrow and peripheral blood myeloid cells, bcr rearrangement was detected in bone marrow and in granulocytes. B cells were stimulated with Epstein-Barr virus (EBV) in order to evaluate involvement of lymphocytes, EBV-transformed lymphoblastoid cells expressed a single G6PD phenotype and therefore probably derived from the leukaemic stem cell. However they had a normal karyotype and a constitutional bcr restriction pattern. Molecular analysis in this case of CML clarifies the differentiative potential of cells belonging to the leukaemic clone, by demonstrating that clonal Ph-negative B cells maintain normal differentiative capacity and have a bcr gene sequence which is not rearranged.
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PMID:Clonal B lymphocytes lack bcr rearrangement in Ph-positive chronic myelogenous leukaemia. 280 77

The leukaemic cells of more than 90% of chronic myelogenous leukaemia (CML) patients and of 10% of acute lymphocytic leukaemia (ALL) patients carry the t(9:22) (q34:q11) translocation which generates the Philadelphia chromosome (Ph1). In CML the abl gene is translocated from chromosome 9 to the centre of the bcr gene on chromosome 22 and this results in production of chimaeric bcr-abl RNA translated into a protein of relative molecular mass (Mr) 210,000 (210K). Our data indicate that in ALL abl is translocated into the 5' region of the bcr gene. The consequence of this is the expression of a fused transcript in which the first exon of bcr is linked to the second abl exon. This transcript encodes a 190K protein kinase.
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PMID:A new fused transcript in Philadelphia chromosome positive acute lymphocytic leukaemia. 282 22

Oncogene abnormalities are thought to have a central role in some human malignant disorders, particularly Burkitt leukaemia/lymphoma and chronic myeloid leukaemia (CML). However, the extent to which specific oncogene changes determine the clinical features of these disorders is unknown. This question was studied in two groups of patients with CML negative for the Philadelphia (Ph) chromosome; one group showed clinical features typical of Ph-positive CML and the other group lacked such features. Molecular findings were compared with those of Ph-positive CML. In all ten patients there was evidence for rearrangement of the bcr (breakpoint cluster region) gene. In the four cases studied the c-abl proto-oncogene was translocated to chromosome 22 and in five cases there was transcription of a chimeric bcr-abl mRNA. Thus, the molecular abnormality is the same in both groups of Ph-negative CML and identical to that in Ph-positive CML. Factors other than the bcr/c-abl rearrangement must underlie the clinical heterogeneity of CML.
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PMID:Do oncogenes determine clinical features in chronic myeloid leukaemia? 288 97

We have determined the prevalence of amplification and rearrangements for c-myc, c-myb, c-mos, bcr, c-abl, c-Ha-ras-1, c-N-ras, and c-K-ras-2 in a total of 51 cases of human leukaemia (19 patients with AML, 13 cases with CML, 14 cases with ALL, and 5 cases with CLL). Amplifications at a level of more than 2 two copies per haploid genome are apparently very rare and were found only once for c-myb in a c-ALL patient. Oncogene rearrangements were not found except for bcr, which was rearranged in all cases of CML, and 5 cases of ALL studied. Restriction fragment lengths polymorphisms (RFLPs) were also analysed. A previously described rare 5 kb EcoRI allele at the c-mos locus was absent in our patients. Rare alleles at the c-Ha-ras-1 locus were found to be significantly more prevalent in our patients than in a control group. Transfection experiments revealed no dominant transforming oncogenes in the tumour DNA of 3 patients carrying such rare alleles.
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PMID:Oncogene amplifications, rearrangements, and restriction fragment length polymorphisms in human leukaemia. 288 56

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

Breakpoints on chromosome 22 in the translocation t(9;22) found in Philadelphia positive acute lymphoblastic leukaemia patients fall within two categories. In the first the breakpoint is localized within the breakpoint cluster region of the BCR gene, analogous to the chromosome 22 breakpoint in chronic myeloid leukaemia. The second category has a breakpoint 5' of this area, but still within the BCR gene. We have previously shown that these breakpoints occur within the first intron of the BCR gene and cloned the 9q+ junction from such a patient. We have now determined the sequences around the breakpoints on both translocation partners from this patient as well as the germline regions. The chromosome 9 ABL sequence around the breakpoint shows homology to the consensus Alu sequence whereas the chromosome 22 BCR sequence does not. At the junction there is a 6 bp duplication of the chromosome 22 sequence which is present both in the 9q+ and in the 22q- translocation products. Possible mechanisms for the generation of the translocation are discussed.
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PMID:Nucleotide sequence of both reciprocal translocation junction regions in a patient with Ph positive acute lymphoblastic leukaemia, with a breakpoint within the first intron of the BCR gene. 291 61

Human chronic myelogenous leukaemia is characterized by a reciprocal translocation between chromosomes 9 and 22 resulting in an abbreviated form of chromosome 22 and the transfer of the abl cellular oncogene from chromosome 9 into the bcr gene of chromosome 22. Characterization of an 8-kilobase RNA specific to chronic myelogenous leukaemia shows it to be a fused transcript of the two genes. The fused protein that would be produced is probably involved in the malignant process.
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PMID:Fused transcript of abl and bcr genes in chronic myelogenous leukaemia. 298 92

The Philadelphia (Ph) chromosome breakpoints in chronic myelocytic leukaemia are clustered on chromosome 22 band q11 in a 5.8-kilobase (kb) region designated bcr. The c-abl protooncogene is translocated from chromosome 9 band q34 into bcr and the biochemical consequence of this molecular rearrangement is the production of an abnormal fusion protein bcr-abl p210 with enhanced protein-tyrosine kinase activity compared to the normal p145 c-abl protein. The Ph chromosome translocation is also seen in some acute lymphoblastic leukaemias with B-cell precursor phenotypes some of which have bcr rearrangement (bcr+) and some do not (bcr-). We present evidence that the Ph+, bcr- leukaemias are associated with a novel p190 abl kinase. We propose that acute lymphoblastic leukaemias that are bcr+, p210+ are probably lymphoid blast crises following a clinically silent chronic phase of chronic myelocytic leukaemia arising in multipotential stem cells whereas bcr-, p190+ cases are de novo acute lymphoblastic leukaemias arising in more restricted precursors.
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PMID:A novel abl protein expressed in Philadelphia chromosome positive acute lymphoblastic leukaemia. 302 81

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

In an attempt to further substantiate the involvement of the c-abl oncogene in the genesis of chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL), we performed in-situ hybridization with the c-abl probe on metaphase chromosomes of a healthy control, a karyotypically normal non-CML leukemia, three cases of CML with t(9;22), t(13;22) and t(3;9;22), one blast phase CML with t(9;22), Ph, + Ph, and one ALL with t(9;22), Ph, + Ph. The aberrant 9q could be cytogenetically identified in all cases except t(13;22). The molecular data clearly demonstrated the involvement of the c-abl in t(13;22) and the karyotype was revised to t(9;13;22). All patients, except the control, showed the altered c-able/bcr rearrangement that has been demonstrated in the Ph-chromosome from the standard t(9;22) translocation. These findings suggest that genomic diversities have important clinical differences in these two diseases. The amalgamation of information from cytogenetic and molecular data on cases where translocations are not precise or difficult to identify, will lead towards a deeper understanding of leukemias.
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PMID:Further evidence of the involvement of the c-abl oncogene in chronic myelogenous leukemia and acute lymphocytic leukemia. 307 67


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