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

Immunogenotypic changes in 32 patients with B-precursor acute lymphoblastic leukemia (ALL), including three patients with t(4;11) and 13 with t(9;22), were determined using immunoglobulin heavy (IgH) chain gene probe and T-cell receptor beta, gamma and delta chain gene probes. Clonogenic assay was performed in 12 of the 32 patients. In this study, four patients had a germline configuration of the IgH chain gene, showing a dissociation between phenotypic and genotypic expression; three patients had Philadelphia-positive (Ph+) ALL. The immunogenotypic manifestation in Ph+ ALL does not depend on whether the leukemia cells had rearrangement within the major breakpoint cluster region (major-BCR) DNA sequence or the leukemia cells had myeloid-associated antigens. Colony assay using various recombinant cytokines demonstrated that the leukemia cells from four of 12 patients formed colonies in response to myelopoietic stimulants; three of the four patients were major-BCR-rearranged Ph+ ALL. Notably, cells from one patient with Ph+ ALL formed colonies on the addition of granulocytic colony-stimulating factor. This indicates not only the biological heterogeneity of ALL cells but also that some of the characteristics of the cells are related to specific chromosome changes.
Leukemia 1992 Apr
PMID:Immunogenotypes and clonal culture analysis in B-precursor acute lymphoblastic leukemia. 158 87

The Philadelphia (Ph) chromosome can be detected in the vast majority of patients with chronic myelogenous leukemia (CML). We performed a long-range analysis of chromosomal translocation junction by pulsed-field gel electrophoresis (PFGE) techniques, to examine whether molecular evidence of a reciprocal Ph translocation exists in Ph-positive CML as well as Ph-negative, M-BCR rearrangement-positive CML. The rearrangement within M-BCR and ABL was detected in all patients including nine Ph-positive CML, and three Ph-negative CML. The rearranged 3'-abl fragments showed comigration with rearranged 5'-bcr fragment in rare-cutting restriction enzyme digests in all patients with Ph-positive CML. Thus, the physical linkage of the 3' part of ABL to the 5' side of M-BCR on 22q-chromosome was shown. The same linkage was also demonstrated in all three patients with Ph-negative CML. Meanwhile, the rearranged 3'-bcr fragments showed comigration with rearranged pHabl5' (or T39-1-2) fragments in all patients with Ph-positive CML, indicating the linkage of the 5' end of ABL to the 3' part of M-BCR on 9q+ chromosome. However, this linkage was absent in two Ph-negative CML patients who could be studied. The results suggest that a genomic insertion of 3' ABL into M-BCR in Ph-negative CML occurs by a single cytogenetic event rather than a two-translocation mechanism.
Leukemia 1992 May
PMID:Absence in Ph-negative, M-BCR rearrangement-positive chronic myelogenous leukemia of linkage between 5' ABL and 3' M-BCR sequences in Philadelphia translocation. 159 4

The Philadelphia (Ph) translocation is the most common cytogenetic abnormality in adult acute lymphoblastic leukemia (ALL) and is associated with an adverse prognosis. Using polymerase chain reaction (PCR) technology we recently observed a remarkably high incidence (55%) of BCR-ABL rearrangements in adult common ALL patients. In the present study we asked whether a subset of Ph-negative cALL, similarly to Ph-negative chronic myelocytic leukemia (CML) patients, exhibit BCR-ABL transcripts. PCR analysis of 58 adult Ph-negative cALL patients, including 47 cases with a normal karyotype revealed no evidence of chimeric BCR-ABL genes. We conclude that Ph-negative BCR/ABL-positive ALL is very rare entity if existing at all.
Leukemia 1992 May
PMID:Polymerase chain reaction analysis of BCR-ABL sequences in adult Philadelphia chromosome-negative acute lymphoblastic leukemia patients. 159 11

The Philadelphia chromosome, originally thought to be associated solely with chronic myelogenous leukemia (CML), has since been identified in acute leukemias and in some cases of lymphoma. The Philadelphia chromosome results from reciprocal translocation of genetic material between chromosome 9 and 22 involving the c-abl and BCR genes respectively. Southern blot analysis of the BCR genes was carried out on biopsy specimens from 49 patients presenting with malignant lymphoma without a previously documented CML phase. In two patients, BCR gene rearrangements were detected in the malignant lymph nodes but not in the bone marrow samples. A third patient showed BCR gene rearrangements in the bone marrow but not in the lymph node. From this limited study, it seems that the overall incidence of BCR gene rearrangement in malignant lymphoma is similar to that observed in adult AML.
Leukemia 1992 Jun
PMID:Rearrangement of BCR genes in malignant lymphoma. 160 94

Therapy with interferon-alpha results in complete cytogenetic remission in 15-20% of patients with chronic myelogenous leukemia. Even during prolonged clinical follow-up, most of these patients do not relapse. However, because of the limited sensitivity of cytogenetic techniques (approximately 5%) and Southern blots (approximately 1%), it is uncertain whether the residual malignant clone becomes extinct or persists below the limit of detection in these patients. We used polymerase chain reaction to amplify the chimeric BCR-ABL transcripts in 18 patients with chronic myelogenous leukemia who became Ph1 chromosome negative while receiving treatment with interferon-alpha, either alone or in combination with interferon-gamma. At the time of study, these patients had been Ph1-negative for a median of 22+ months. Fifteen patients were positive for residual BCR-ABL transcripts. No residual BCR-ABL message was detected on analysis of multiple serial samples in three patients. In order to confirm these results, the samples from these three patients, along with positive and negative controls, were analyzed by two independent laboratories in a blinded fashion. In the first laboratory, RNA specimens from all three patients were considered negative using chemiluminescent acidinium-ester-labeled probes. In the second laboratory, samples from all three patients were also negative by conventional polymerase chain reaction (PCR). However, when a second round of amplification was carried out on the amplified samples using a different combination of primers, samples from two of the three patients were positive. The results confirm the presence of a small proportion of BCR-ABL-positive cells in the majority of patients who are in complete remission and highlight some of the potential problems of PCR-based analysis. There is a need to standardize PCR methodology and potential confounding factors need to be addressed before PCR can be generally applied to analysis of minimal residual disease in CML. The implications of BCR-ABL positivity for these patients are discussed.
Leukemia 1992 Aug
PMID:Minimal residual disease in interferon-treated chronic myelogenous leukemia: results and pitfalls of analysis based on polymerase chain reaction. 164 Jul 25

Pulsed field gel electrophoresis was used to construct a long-range map of the normal BCR gene. A single BssHII restriction fragment encompasses all the known exons of the BCR gene (except a small 5' part of exon one). MIuI has one restriction site within the first intron of the BCR gene and another 250 kb downstream. This MIuI fragment contains most of the BCR gene coding sequences apart from the first exon and contains more sequences downstream of the BCR gene than the BssHII fragment. The NarI restriction sites are very close to the BssHII sites in the BCR gene, but they differ in the ABL gene, so that NarI digests could theoretically provide additional information in chronic myeloid leukaemia (CML) patients. This map was used to confirm BCR gene involvement in two CML patients in whom results of conventional Southern blotting of DNA were ambiguous. It was also used in a third patient to demonstrate the presence of a breakpoint apparently outside the BCR gene. Preliminary evidence from the use of PFGE confirms the presence of three BCR-related genes homologous to 3' sequences in the classical BCR gene (BCR-1). These BCR-related genes are located at a considerable distance from BCR-1.
Leukemia 1991 Jul
PMID:Long-range mapping of the normal BCR gene. 164 56

Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL) is most common in adults and is associated with poor prognosis. Since karyotypic identification of the Philadelphia translocation has been hampered by technical difficulties, we used the polymerase chain reaction (PCR) to look for the BCR-ABL rearrangement in stored samples from a selected group of 314 German ALL patients. BCR-ABL transcripts were found in 77 of 179 adults and were restricted to those with B-precursor leukaemias. 55% of adult common ALL patients had BCR-ABL and its presence correlated with poor overall survival and remission duration. Of 135 children with common ALL, 5 (6%) primary cases and 8 (17%) with recurrent neoplasias were PCR-positive. We recommend prospective evaluation of BCR-ABL analysis with PCR in patients with a B-precursor leukaemia.
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PMID:Detection of chimeric BCR-ABL genes in acute lymphoblastic leukaemia by the polymerase chain reaction. 168 8

The region of greatest rupture of the gene BCR (M-bcr) was analysed with the restriction enzyme Bgl II plus a molecular probe containing the 5' end of M-bcr in a woman with atypical, Ph'-negative chronic myelogenous leukaemia. An abnormal DNA fragment of 5.0 kb and an extra band were found, suggesting rearrangement. Nevertheless, the use of several restriction enzymes and the addition of a different probe showed the existence of polymorphism with the enzyme Bgl II, which is an unusual finding. These findings stress the usefulness of using different restriction enzymes and molecular probes in the molecular study of chronic myelogenous leukaemia.
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PMID:[Atypical chronic myeloid leukemia with polymorphism of the BCR gene]. 168 92

The Philadelphia chromosome defines chronic myeloid leukemia, and is mostly based on a translocation t(9;22) with a typical BCR-ABL rearrangement which also occurs in so called atypical translocations. The transformation of chronic myeloid leukemia is associated with clonal evolution in 80% of cases. The appearance of an isochromosome 17q unequivocally heralds the onset of a myeloid type of blast crisis. Treatment of Ph-positive CML has still to be considered palliative except for allogeneic bone marrow transplantation. The Philadelphia chromosome is also found in about 20% of patients with acute lymphoblastic leukemia and in about 2% of patients with nonlymphoblastic leukemia. It is associated with a poor prognosis. Molecular and cytogenetic findings help differentiating between de novo acute leukemia and blast crisis of chronic myeloid leukemia.
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PMID:[Cytogenetic and clinical features of Philadelphia chromosome positive leukemias]. 170 14

Joining of the BCR and ABL genes is an essential feature of the group of human leukemias characterized by the Philadelphia chromosome and there is recent evidence that the human BCR-ABL fusion gene induces leukemia in experimental animals. Joining of these two genes is the result of cytogenetic translocation, usually the t(9;22)(q34;q11), but sometimes of more complex translocations involving one or more chromosomes in addition to chromosomes 9 and 22. The leukemic cells of some patients carry the BCR-ABL fusion gene but have an apparently normal karyotype. Recent studies show that these cells conceal complex chromosome rearrangements. Because the BCR-ABL fusion gene appears to be the result of cytogenetic rearrangement in all cases of these leukemias, the causes and mechanism of chromosome rearrangement will be relevant to the development of leukemia in man. We examine mechanisms of chromosome rearrangement and propose that both simple and complex chromosome translocations result from a single, though sometimes complex, interchange event.
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PMID:Complex chromosomal translocations in the Philadelphia chromosome leukemias. Serial translocations or a concerted genomic rearrangement? 175 91


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