1/12. 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 = acid (Clic here for more details about this article) |
2/12. Common germinal-center B-cell origin of the malignant cells in two composite lymphomas, involving classical Hodgkin's disease and either follicular lymphoma or B-CLL.BACKGROUND: Classical Hodgkin's disease (HD) and B-cell non-Hodgkin lymphoma (NHL) occasionally occur in the same patient. Such composite lymphomas represent interesting models to study the pathogenesis of B-cell lymphomas and the relationship between HD and B-cell NHL. MATERIALS AND methods: We analyzed two composite lymphomas (a combination of classical HD with follicular lymphoma [FL] and a combination of classical HD with B-cell chronic lymphocytic leukemia [B-CLL]) by micromanipulation of single cells from tissue sections and amplification of immunoglobulin V region genes for the clonal relationship of the tumor cells. RESULTS: In both cases, clonally related variable (V) genes with both shared as well as distinct somatic mutations were obtained from the two lymphomas, showing that in each of the cases the distinct tumor cells were members of a common germinal center (GC) B-cell clone. FL cells from two different lymph nodes of patient 1 showed a similar mutation pattern, suggesting that infiltration of these lymph nodes by tumor cells was not restricted to a particular FL cell or subclone. In the FL, a single cell was identified with a mutation signature indicating that premalignant cells can persist in the tissue. CONCLUSIONS: The cases presented here further underline the close relationship between HD and B-cell NHL and the role of the GC in lymphomagenesis. Whereas the latter was already suggested for FL and HD, the present study indicates that also in the B-CLL subset characterized by mutated Ig genes, important steps in malignant transformation happen in the GC, and that HRS cells can derive from CD5-positive B cells.- - - - - - - - - - ranking = 29485.700468592keywords = amplification (Clic here for more details about this article) |
3/12. 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 = 88457.101405774keywords = amplification (Clic here for more details about this article) |
4/12. Severe lactic acidosis due to thiamine deficiency in a patient with B-cell leukemia/lymphoma on total parenteral nutrition during high-dose methotrexate therapy.An 11-month-old girl with B-cell leukemia/lymphoma developed profound lethargy due to severe lactic acidosis during chemotherapy and total parenteral nutrition (TPN). Initial treatment with NaHCO3 was ineffective. Treatment with a vitamin cocktail (OH-cobalamin, pyridoxine, thiamine, riboflavine, biotin, carnitine) at pharmacologic doses rapidly improved the child's clinical and laboratory status. Lactic acidosis was caused by an impairment of pyruvate dehydrogenase complex, which was due to lack of its necessary cofactor thiamine in the TPN. This case report indicates that lactic acidosis may be a front-line diagnosis in patients on TPN with lethargy and outlines the need for monitoring thiamine supply in TPN.- - - - - - - - - - ranking = 7keywords = acid (Clic here for more details about this article) |
5/12. Defective collagen-induced platelet activation in two patients with malignant haemopathies is related to a defect in the GPVI-coupled signalling pathway.The occurrence of a thrombocytopathy concomitantly to the development of a malignant haemopathy has been reported for some time, but little is known about the mechanism(s) involved in the platelet dysfunction. Platelet glycoprotein VI (GPVI) has now been identified as a principal platelet receptor for collagen. In this paper, we report the cases of two patients with a myelodysplasia and a B lymphopathy, respectively, who presented with thrombocytopathy in relation to a defective GPVI-mediated platelet reactivity to collagen. Thus, with regard to the different steps of adhesion, activation secretion or aggregation, patients' platelet responses to collagen and to the GPVI specific agonists, collagen related peptide (CRP) or convulxin were null or dramatically impaired. Platelet responses to other agonists ADP, TRAP, arachidonic acid were normal or showed only a moderate decrease. GPVI content was repeatedly normal, and binding of specific ligands, such as convulxin, satisfactory. Nevertheless, specific activating monoclonal antibodies and convulxin failed to induce platelet secretion; collagen, CRP or convulxin were unable to provoke calcium mobilisation. Furthermore, using a perfusion chamber model, we showed that ex vivo collagen-induced thrombi formation was very impaired. Taken together, these data provide evidence, for the first time, of an acquired defect in GPVI-mediated platelet reactivity to collagen, which reflects data observed in constitutional GPVI deficiencies, in two patients with malignant haemopathies.- - - - - - - - - - ranking = 1keywords = acid (Clic here for more details about this article) |
6/12. association of a mature B cell leukemia with a 4p chromosomal abnormality: derivation and characterization of a cell line.We have found a single 4p chromosomal abnormality, 46,XX, -4, der(4)t(3;4)(q13.3;p16), in a patient with an unusual B cell leukemia of mature phenotype characterized by a high white cell count, tartrate-resistant acid phosphatase-positive malignant cells, splenic white pulp proliferation, and a serum IgM monoclonal gammopathy. The malignant cells were characterized by surface expression of CD19 (B4), CD20 (B1), IgM, IgD, kappa, and HLA-DR. They were weakly positive for CD21 (B2) and negative for CD25 (interleukin-2 receptor). The malignant cells also showed clonal rearrangement of the immunoglobulin heavy chain and kappa light chain genes. A cell line, designated HCLW-3B, was derived from unstimulated peripheral blood obtained during the leukemic phase and was found to contain the same 4p chromosomal abnormality as well as genomic sequences of the Epstein-Barr virus nuclear antigen. A somatic cell hybrid constructed from HCLW-3B containing the derivative chromosome 4 was used to confirm that chromosome 3q was the source of the translocated material. The availability of a cell line which is clonally derived from the patient's circulating leukemia cells should permit further characterization of this translocation at the molecular level.- - - - - - - - - - ranking = 1keywords = acid (Clic here for more details about this article) |
7/12. A CD5 leukemic lymphoma with monocytoid features: an unusual B-cell lymphoma mimicking hairy-cell leukemia.A case of lymphoma presenting with features shared by hairy cell leukemia (HCL) and its variant, intermediate lymphocytic lymphoma (ILL) and monocytoid B-cell lymphoma (MBCL) is described. Clinical presentation and the morphological findings observed in peripheral blood and in bone marrow biopsy suggested an HCL; however, the tartrate-resistant acid phosphatase negativity of peripheral blood lymphocytes, the histologic pattern observed in the spleen, and the immunophenotyping of peripheral blood, spleen and bone marrow neoplastic lymphocytes (expression of CD5 and lack of CD25), were strongly against this hypothesis. The clinical course was aggressive. This report emphasizes the concept of the equivocal presentation of some 'low-grade' B-cell lymphomas. It is further pointed out that, even with complete and exhaustive morphological and immunological analyses, atypical cases may be encountered.- - - - - - - - - - ranking = 1keywords = acid (Clic here for more details about this article) |
8/12. Leukemic meningitis in a patient with splenic lymphoma with villous lymphocytes (SLVL). meningitis as a possible initial manifestation of SLVL.BACKGROUND. Splenic lymphoma with villous lymphocytes (SLVL) is a low grade, non-Hodgkin's lymphoma with a stable or slowly progressive clinical course. To the authors' knowledge, central nervous system involvement has not been described previously in patients with SLVL. methods. Morphologic, immunocytochemical, and immunohistochemical analyses were conducted to determine the nature of villous lymphocytes in the peripheral blood, spleen, and cerebrospinal fluid (CSF) of a patient with massive splenomegaly. RESULTS. A diagnosis of SLVL was made, based on tartrate-resistant acid phosphatase-negative peripheral villous lymphocytosis with CD19 , CD20 , HLA-DR phenotypes, and the involvement of spleen white pulp with these cells. Mononuclear cells in the CSF showed the same morphologic and immunocytochemical features seen in the villous lymphocytes in the peripheral blood and spleen. splenectomy and intrathecal chemotherapy were successful in clearing leukemic cells from the CSF. CONCLUSION. In this patient with SLVL in whom leukemic meningitis developed, meningitis was found to be a possible initial manifestation of SLVL.- - - - - - - - - - ranking = 1keywords = acid (Clic here for more details about this article) |
9/12. B-cell prolymphocytic leukemia expressing discordant myeloid-associated antigens in simultaneous specimens from bone marrow and peripheral blood.The case of a 73-year-old man with B-cell prolymphocytic leukemia (PLL) and rapid clinical demise is reported. Flow cytometric immunophenotyping results of specimens obtained from the patient demonstrated a monoclonal CD5 positive B-cell population with myeloid-associated marker expression, which was discordant: CD15 and CD11b were expressed in bone marrow leukemic cells, whereas peripheral blood leukemic cells showed virtually no expression of these markers. Discordant immunophenotyping results between bone marrow and peripheral blood cells have been reported recently. Additionally, investigators have associated expression of CD13 and CD11b by chronic B-cell lymphoid leukemias with a more aggressive clinical course and shorter survival. Expression of these myeloid-associated antigens by B-cell prolymphocytes in PLL has not been widely reported. cytogenetic analysis revealed a karyotype of 46,XY/?44,XYdel(1q),del (3p), whereas molecular genetic studies demonstrated immunoglobulin gene rearrangements in both heavy and light chain regions. Cytochemical staining for PAS (periodic acid-Schiff), nonspecific esterase and methyl-green-pyronin was positive in leukemic cells.- - - - - - - - - - ranking = 1keywords = acid (Clic here for more details about this article) |
10/12. 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 = 176914.20281155keywords = amplification (Clic here for more details about this article) |
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