1/8. B cell prolymphocytic leukaemia (B-PLL) with complex karyotype and concurrent abnormalities of the p53 and c-MYC gene.We report the cytogenetic, molecular and biological characterization of a case of B-PLL with a complex karyotype and concurrent abnormalities on the p53 and c-MYC genes. Conventional cytogenetics suggested that both 17q arms were translocated to chromosomes 1q and 14p, respectively, whereas both 17p arms were not identified. In addition, a Burkitt's-like variant translocation t(2;8) was found. Study of loss of heterozygosity at 17p13 and p53 direct sequencing demonstrated the presence of only one copy of the p53 gene. A 27 bp deletion in exon 8 that resulted in the expression of a p53 protein lacking nine amino acids from the dna binding region was also found. To confirm the presence of one copy of the p53 gene and localize it, fluorescent in situ hybridization (FISH) studies using a p53 gene probe was performed. Only one signal of p53 was visualized. Moreover, the DAPI profile of the chromosome containing the hybridization spot for the p53 probe did correspond to the cytogenetic marker identified as der(14)t(14;17). Whole chromosome 14 paint, centromere-specific for chromosome 17 and p53 gene probes were cohybridized to the preparations. This demonstrated that the der(14) contained the 17 centromere and distally the p53 gene suggesting that the der(14) contained the short arm of chromosome 17 with the breakpoint occurring in the long arm. FISH studies confirmed the involvement of c-MYC and KAPPA in the t(2;8) translocation. To our knowledge, this is the first case of B-PLL with inactivation of the p53 gene by mutation together with a Burkitt's-like t(2;8) translocation involving the c-MYC gene. The cooperation of these genes may have conferred a growth advantage which was critical in the development of this aggressive form of B-PLL.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/8. Unusual case of leukemic mantle cell lymphoma with amplified CCND1/IGH fusion gene.We describe a case of leukemic mantle cell lymphoma (MCL) with complex karyotype and amplification of the CCND1/IGH fusion gene. Testing for the presence of t(11;14), the hallmark of MCL, revealed multiple copies of the fusion signals. We therefore conducted extensive molecular cytogenetic studies to delineate the nature and consequences of such an abnormality. We localized the amplification to the der(14)t(11;14) and to a der(2) chromosome in a form of interspersed chromosome 11 and 14 material. This resulted in high expression of cyclin d1 mRNA and the protein expressed independently of the cell cycle phase. CGH analysis revealed that the overrepresentation on chromosome 11 included chromosomal band 11q23 in addition to the CCND1 locus at 11q13. The band 11q23 harbors the ataxia telangiectasia mutated (ATM) gene recently proposed to be involved in the pathogenesis of MCL with high incidence of deletions in this locus. Using YAC 801e11, containing the ATM gene, we demonstrated several hybridization signals, suggesting that this region also formed part of the amplicon. This case also showed TP53 gene abnormalities: protein expression, monoallelic deletion, and a mutation in exon 5. The clinical course was aggressive, and the patient died within 6 months of presentation. This is to our knowledge the first description of amplification of the CCND1/IGH fusion gene in a human neoplasm, which may have played a role in the fulminating course of the disease in this patient.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
3/8. Mature B-cell leukemias with more than 55% prolymphocytes: report of 2 cases with burkitt lymphoma-type chromosomal translocations involving c-myc.CONTEXT: The molecular genetic events involved in the pathogenesis of mature B-cell leukemias with more than 55% prolymphocytes are not well characterized. We have encountered 2 such cases in which conventional cytogenetic analysis identified burkitt lymphoma-type chromosomal translocations involving 8q24. OBJECTIVE: To assess these 2 cases for involvement of the c-myc gene using fluorescence in situ hybridization analysis with probes specific for the c-myc and immunoglobulin heavy-chain (IgH) genes. RESULTS: In both cases, conventional cytogenetic analysis demonstrated complex karyotypes, including chromosomal translocations involving 8q24. In case 1, a case of de novo prolymphocytic leukemia, the t(8;14)(q24;q32) was detected. In case 2, a case of chronic lymphocytic leukemia in prolymphocytoid transformation, the t(8;22)(q24;q11) was identified. fluorescence in situ hybridization studies showed c-myc/IgH fusion signals in case 1, proving the presence of the t(8;14). Split c-myc signals without fusion to IgH were observed in case 2, proving c-myc gene rearrangement and consistent with the t(8;22). CONCLUSION: These results suggest that c-myc gene alterations may be involved in the pathogenesis of a subset of mature B-cell leukemias with more than 55% prolymphocytes.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/8. Successful treatment of B-cell prolymphocytic leukemia with monoclonal anti-CD20 antibody.We report a patient with B-cell prolymphocytic leukemia (PLL) who was treated successfully with the monoclonal anti-CD20 antibody (rituximab). The patient had recurrent infections due to relative neutropenia, secondary to bone marrow infiltration. After treatment with monoclonal anti-CD20 antibodies (rituximab) 375 mg/m(2) weekly for 4 weeks, complete remission was obtained. It was documented by normalization of peripheral blood counts, disappearance of organomegaly, and by molecular cytogenetics-fluorescent in situ hybridization (FISH) on bone marrow cells. She remains in complete remission 8 months following the discontinuation of treatment. This is the second reported case of successful treatment of B-cell PLL with rituximab.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
5/8. Translocation (8;14)(q24;q32) as the sole cytogenetic abnormality in B-cell prolymphocytic leukemia.B-cell prolymphocytic leukemia is a relatively rare lymphoproliferative disorder. No specific cytogenetic abnormality has yet been associated with it. The most common translocation reported in patients with this disease is t(11;14)(q13;q32). We describe the case of a patient with B-cell prolymphocytic leukemia and a hitherto unreported genetic translocation (8;14)(q24;q32) as the sole genetic abnormality, classically seen in patients with B-cell acute lymphoblastic leukemia/burkitt lymphoma. This patient presented with an asymptomatic leukocytosis and splenomegaly. Her marrow showed lymphoid hyperplasia, with immunophenotyping consistent with prolymphocytic leukemia; however, t(8;14)(q24;q32) was the only cytogenetic aberration with both standard karyotyping and fluorescence in situ hybridization analysis.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
6/8. Establishment of a leukemia cell line with i(12p) from a patient with a mediastinal germ cell tumor and acute lymphoblastic leukemia.We report the establishment of a leukemia cell line (UoC-B10) from a patient who developed leukemia several months after the diagnosis of a mediastinal yolk sac tumor. The patient's yolk sac tumor responded to combination chemotherapy, and a mature teratoma with focal areas of hematopoiesis was subsequently resected. However, 5 months after the initial diagnosis, the patient developed an acute lymphoblastic leukemia with a precursor B-cell phenotype. cytogenetic analysis showed an i(12p) abnormality in the patient's leukemia cells and in the UoC-B10 cell line. The i(12p) was also identified retrospectively in the mediastinal tumor cells by fluorescent in situ hybridization analysis. The UoC-B10 cell line, which has been growing continuously for > 24 months in culture, was Epstein-Barr virus negative and was generally concordant with the patient's leukemia cells by analysis of immunophenotype, karyotype, and genotype. The UoC-B10 cell line possesses receptors for granulocyte-colony-stimulating factor, a cytokine which the patient received as part of his treatment protocol. This cell line may be useful in studying the relationship between i(12p) and hematological differentiation of human mediastinal germ cell tumors.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
7/8. Partial chromosome 21 amplification in a child with acute lymphoblastic leukemia.monosomy 21 and metacentric markers corresponding in size to chromosomes 8 to 12 were found as the only clonal chromosomal changes in a child with acute lymphoblastic leukemia (ALL). chromosome painting with a whole chromosome 21-specific probe showed that the marker originated from chromosome 21. fluorescence in situ hybridization with yeast artificial chromosome (YAC) probes to chromosome 21 showed genomic amplification with two, four, or more copies of the probed dna sequences present on the marker. The most amplified regions of chromosome 21 were centromeric and telomeric to the Down's syndrome region. This observation supports the notion that amplification of only parts of chromosome 21 may be important in the leukemogenic process in spite of the high incidence of complete trisomy 21 in ALL.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |
8/8. Richter's syndrome in a case of atypical chronic lymphocytic leukaemia with the t(11;14)(q13;q32): role for a p53 exon 7 gene mutation.Clinicobiological, histological, cytogenetic and molecular genetic studies were performed in a case of atypical B-cell chronic lymphocytic leukaemia (B-CLL) with the t(11;14)(q13;q32) evolving into Richter's syndrome (RS) in order (a) to determine the clonal relationship between the cell of origin for B-CLL and RS, and (b) to analyse genetic events underlying the disease progression in this patient. After 4 years following diagnosis, a rapid deterioration of the clinical picture occurred, concomitant with the appearance of large lymphoid blasts in peripheral blood (PB), bone marrow (BM) and ascites samples. A diagnosis of RS was made and cytogenetic analysis revealed karyotype evolution with trisomy 7 and del(17p) in addition to t(11;14). fluorescence in situ hybridization showed 78% lymphoid blast cells obtained from ascites sample to be trisomic using a chromosome-7-specific pericentromeric probe. Whereas no rearrangement of the c-myc proto-oncogene was detected at disease progression, direct sequencing of p53 gene exon 5-9 revealed an exon 7 missense point mutation. This abnormality was not present in the CLL phase. Immunological staining with the monoclonal antibody PAb-1801, detecting the p53 protein product, revealed a negative pattern in the CLL phase, whereas 24% positivity was documented in representative samples obtained at RS. It is concluded that RS was cytogenetically related with B-CLL in this patient, suggesting the occurrence of a bona fide transformation and that the mutation of p53 exon 7, in association with the development of 17p deletion, possibly played a role in the development of RS.- - - - - - - - - - ranking = 0.5keywords = hybridization (Clic here for more details about this article) |