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

We have analyzed the oncogene rearrangements involving BCL2 and MYC in the leukemia cells of a patient with an aggressive prolymphocytic leukemia that had an abnormal karyotype including a t(14;18) translocation and a chromosome 17q+. Molecular analysis showed that BCL2 was rearranged in the major breakpoint cluster region and had joined into the immunoglobulin heavy chain gene as in follicular lymphoma. Cloning and sequence analysis of the rearranged MYC gene revealed that MYC was truncated at the Pvu II site at the end of the first exon of MYC and had joined into the regulatory elements of a gene that we called BCL3 (B-cell leukemia/lymphoma 3). The BCL3 locus was mapped to chromosome 17 band q22. We found BCL3 transcribed as a message of 1.7 kilobases in many hematopoietic cell lines representing all hematopoietic lineages. In the patient's leukemia cells, the truncated MYC gene was highly expressed under the influence of BCL3 regulatory elements, leading to an aggressive B-cell leukemia that presumably had been derived from an indolent lymphoma carrying a rearranged BCL2 gene.
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PMID:Activation of MYC in a masked t(8;17) translocation results in an aggressive B-cell leukemia. 268 63

The t(14;19) is a recurring translocation found in a small number of cases of chronic B-cell leukemia (CLL). We have cloned and sequenced the breakpoint in a patient with a t(14;19) and shown that the breakpoint on chromosome 14 occurred in the C mu switch region, and that the breakpoint on chromosome 19 occurred in the 5' untranslated region of the BCL3 gene. This is in contrast to all the other reported cases with a t(14;19) in which the breakpoints on chromosome 14 occurred in the C alpha 1 or C alpha 2 switch region, and the breakpoints on chromosome 19 occurred upstream of the BCL3 gene. Our results further emphasize the importance of the switch region in the t(14;19) translocation.
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PMID:Cloning and sequencing of a t(14;19) breakpoint that involves the C mu switch region. 769 Nov 60

The t(14;19)(q32;q13) is a recurring translocation found in some patients with chronic lymphocytic leukemia (CLL), and the t(14;19) juxtaposes the BCL3 gene on chromosome 19 with the immunoglobulin heavy chain gene (IGH) locus on chromosome 14. Genomic DNAs from 49 patients with chronic B-cell leukemia and the related lymphomas were examined by Southern blot hybridization using 2 separate probes, named p alpha 1.4P and p alpha .5B, from the BCL3 gene locus. None of the 18 patients with leukemic manifestations of non-Hodgkin's lymphomas had detectable BCL3 rearrangements. Of 31 patients with CLL, 2 had the BCL3 rearrangements. A comigration study using the C alpha and C epsilon constant gene probe from IGH indicated that the t(14;19) translocation occurred in these 2 patients, and they were diagnosed with CLL/prolymphocytic (PL) according to the French-American-British (FAB) classification. Probes for the IGH locus revealed that leukemia cells of the 2 patients each were clonal, indicating that both small lymphocytes and prolymphocytoid cells found in the peripheral blood of one patient had the t(14;19), as well as a major population of the small lymphocytes in the peripheral blood of a second patient. It thus appears that tumor cells carrying the t(14;19) constitute a distinct disease entity in a group of chronic B-cell leukemia, that has a converting potential to more aggressive forms.
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PMID:Involvement of the BCL3 gene in two patients with chronic lymphocytic leukemia. 801 90

The t(14;19)(q32;q13) is a recurring translocation found in leukemic cells of some patients with chronic lymphocytic leukemia (CLL). The BCL3 gene was identified on chromosome 19 adjacent to the breakpoint of the translocation, and has been proposed to be a candidate proto-oncogene which may play a role in leukemogenesis. The current study of a Japanese patient with CLL revealed that the (14;19) is reciprocal at the molecular level; the BCL3 gene was juxtaposed to the 5' side of the S alpha 1 switch region of the immunoglobulin heavy chain gene (IGH) on the der(14) chromosome, and the IGH gene 5' to the S alpha 1 region was joined to chromosome 19 sequences on the der(19) reciprocal partner chromosome. The breakpoint on chromosome 19 was 16 kb upstream of the first exon of the BCL3 gene and 7 bp of chromosome 19 sequences were deleted at the point of the junction. The t(14;19) translocations so far molecularly analyzed consistently occurred within one of the two S alpha switch regions; however, sequence analysis of the chromosome 19 regions involved in the translocation failed to demonstrate an obvious sequence similarity with the switch region. The chromosomal breaks on chromosome 19 from two CLL patients having the t(14;19) were within Alu repeated sequences.
Leukemia 1993 Dec
PMID:Molecular characterization of the t(14;19)(q32;q13) translocation in chronic lymphocytic leukemia. 825 6

Junctional sequences created by chromosomal translocations in mature B-cell neoplasms, which involve immunoglobulin gene loci (IG) and putative proto-oncogenes on reciprocal partner chromosomes, are unique to neoplastic cells characterized by particular histological and immunological phenotypes. To establish a rapid and sensitive method to detect neoplastic cells carrying a specific chromosomal translocation, we have developed a novel strategy based on long-distance polymerase chain reaction (LD-PCR) amplification. Genomic DNA was extracted from tumor cells carrying t(14;19)(q32;q13), t(8;14)(q24;q32), t(3;22)(q27;q11), t(2;3)(p12;q27), or t(3;14)(q27;q32). Thirty-two to 35-mer oligonucleotide primer pairs were designed to be complementary to exons or flanking sequences of the BCL3, c-MYC and BCL6 oncogenes, and to IG constant region genes. LD-PCR with a newly available Taq polymerase for longer product synthesis successfully amplified fragments representing BCL3/C alpha junctional sequences for t(14;19); c-MYC/C mu, c-MYC/C gamma, and c-MYC/C alpha for t(8;14); BCL6/C lambda for t(3;22); BCL6/C kappa for t(2;3); 5'-BCL6/C mu, and 5'-BCL6/C gamma for t(3;14). In Burkitt's lymphoma/leukemia, all materials in which c-MYC rearrangements were detectable by conventional Southern blot hybridization showed positive LD-PCR amplification. The sizes of the amplified fragments varied from 1.8 kb to 12 kb, and these were specific to each material. Serial dilution of tumor cells or DNA in negative materials demonstrated a single band on agarose gel electrophoresis stained with ethidium bromide at a level of sensitivity of 10(-3), and hybridization with radioactive probe improved the level by one order of magnitude (1 cell in 10(4)), indicating that this LD-PCR approach is a sensitive technique capable of detecting minimal residual disease. Thus, the present study provided a useful tool for diagnosis and subsequent management of B-cell neoplasms characterized by specific chromosomal translocations.
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PMID:Application of long-distance polymerase chain reaction to detection of junctional sequences created by chromosomal translocation in mature B-cell neoplasms. 870 58

Cytogenetic analysis of patients with chronic B-cell leukemia (B-CLL) indicates that 50% have chromosome abnormalities, while fluorescence in situ hybridization (FISH) and molecular techniques reveal an even higher incidence. Trisomy 12 and deletions or translocation of chromosome 13q14 are the most common abnormalities, but in neither case has the gene or genes involved in the abnormalities been identified. Combined FISH and immunophenotyping studies suggest that both abnormalities are secondary events in B-CLL. Other recurring chromosome abnormalities include 6q-, 11q- and 12p-, but the genes involved in these abnormalities have not been identified. Involvement of the BCL1, BCL2, and BCL3 genes has been reported, but the numbers are low and the cases tend to be atypical. Trisomy 12 in association with complex karyotypic abnormalities is associated with a poor prognosis, and FISH studies show a strong correlation between trisomy 12, atypical morphology, and advanced disease. Ten to 15% of patients have mutations of p53 which is associated with advanced disease, resistance to treatment, and poor survival.
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PMID:Genes and chromosomes in chronic B-cell leukemia. 907 90

Twelve patients with diagnosis of B-cell non-Hodgkin's lymphoma/leukemia and del[7q] were studied for their clinical, cytogenetic, and molecular characteristics. Eleven patients were classified as small cell lymphoma whereas one had a diffuse large cell lymphoma. Lymphoplasmacytic features were observed in six out of eleven small cell lymphomas. Morphologically and immunologically these small cell lymphomas could be classified as chronic lymphocytic leukemia (typical or atypical; 4 cases), marginal zone lymphoma (splenic lymphoma with villous lymphocytes; 1 case), mantle cell lymphoma (2 cases), or nonspecified, non-Hodgkin's lymphoma (4 cases). Eleven of twelve patients presented with peripheral blood and bone marrow involvement. Two of twelve cases showed del[7q] as the sole anomaly. Two different types of deletions were present: ten cases had del(7)(q21q31) and two cases had del(7)(q31q34). Cases that could be molecularly investigated did not show any involvement of BCL2, BCL3, or BCL6, and only one case had BCL1 rearrangement. The data indicate that del(7q) is associated with a subset of mature small B-cell lymphoproliferative disorders of which some but not all show lymphoplasmatic features.
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PMID:del(7q) in chronic B-cell lymphoid malignancies. 907 99

To establish a rapid and sensitive method to detect neoplastic cells carrying a specific chromosomal translocation in B-cell lymphoma/leukemia, we have developed a novel strategy based on long distance polymerase chain reaction (LD-PCR) amplification. Genomic DNA were extracted from tumor cells carrying a t(14;19)(q32;q13), a t(8;14)(q24;q32), a t(3;22)(q27;q11), a t(2;3)(p12;q27), and a t(3;14)(q27;q32). Oligonucleotide primer pairs were designed to be complementary to exons or flanking sequences of the BCL3, c-MYC and BCL6 oncogenes, and to constant region genes of the IG genes. LD-PCR with a newly available Taq polymerase for longer product synthesis successfully amplified fragments representing BCL3/C alpha junctional sequences for t(14;19); c-MYC/C mu, c-MYC/C gamma and c-MYC/C alpha for t(8;14); BCL6/C lambda for t(3;22); BCL6/C kappa for t(2;3); 5'-BCL6/C mu and 5'-BCL6/C gamma for t(3;14), respectively. The sizes of the amplified fragments were varied from 1.8 kb to 12 kb, which were specific to each material. Present study provides a useful tool for diagnosis and subsequent management of B-cell lymphoma/leukemia characterized with specific chromosomal translocation.
Leukemia 1997 Apr
PMID:Long distance polymerase chain reaction for detection of chromosome translocations in B-cell lymphoma/leukemia. 920 76

B cell chronic lymphocytic leukemia (CLL) lacks a consistent genetic abnormality. However, immunoglobulin V(H) gene segment mutation analysis has provided insights into the pathogenesis of these diseases and allowed the development of powerful prognostic markers. Immunoglobulin gene chromosomal translocations are rare in CLL and involve a distinct subset of genes including BCL3, BCL11A and CCND2. BCL2 translocations in CLL appear to arise via a different mechanism from comparable translocations seen in B cell non-Hodgkin lymphoma.
Leukemia 2002 Jun
PMID:The configuration of the immunoglobulin genes in B cell chronic lymphocytic leukemia. 1204 Apr 29

The t(14;19)(q32;q13), involving the BCL3 locus at chromosome 19q13 and the immunoglobulin heavy chain gene at 14q32, is a rare recurrent cytogenetic abnormality identified in B-cell neoplasms, most of which have been classified as chronic lymphocytic leukaemia (CLL) in the literature. We describe the clinicopathological, immunophenotypic and cytogenetic findings in seven patients with B-cell neoplasms associated with t(14;19)(q32;q13). There were five men and two women, with a median age of 48 years (range 33-68). All had absolute lymphocytosis, six had lymphadenopathy, and one had splenomegaly. Lymphocytes in blood and bone marrow aspirate smears were predominantly small and cytologically atypical. Flow cytometric immunophenotyping showed an atypical immunophenotype with low CLL scores. The growth pattern in bone marrow biopsy specimens was interstitial to diffuse; immunohistochemical stains were positive for bcl3 and negative for cyclin D1. Lymph node biopsy specimens of two patients revealed total architectural effacement by neoplasm with proliferation centres. In addition to t(14;19), cytogenetic studies demonstrated trisomy 12 in five patients. These results suggest that B-cell neoplasms with the t(14;19)(q32;q13) present frequently as leukaemia composed of small B-lymphocytes and share many features with CLL. However, these neoplasms also differ from CLL cytologically and in their immunophenotype.
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PMID:The t(14;19)(q32;q13)-positive small B-cell leukaemia: a clinicopathologic and cytogenetic study of seven cases. 1837 8


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