Cytogenetic analysis of 363 consecutively ascertained diffuse large B-cell lymphomas

Cigudosa, Juan C.; Parsa, Nasser Z.; Louie, Diane C.; Filippa, Daniel A.; Jhanwar, Suresh C.; Johansson, Bertil; Mitelman, Felix; Chaganti, R. S. K.

doi:10.1002/(sici)1098-2264(199906)25:2<123::aid-gcc8>3.0.co;2-4

Cited by 155 publications

(99 citation statements)

References 57 publications

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“…She was treated with chlorambucil and subsequently with intravenous fludarabine but failed to respond to either and died with progressive disease in October 1995. Cytogenetics of this case showed 46,XX,t(2;14)(p13;q32) [14]/46,idem,t(3;6)(p21;q25),del(11)(q22q23) [2]/ 46,idem,add(8)(p23) [2] indicating that t(2;14)(p13;q32) was the primary cytogenetic abnormality. Patient 4 presented in February 1986 with generalized lymphadenopathy, hepatosplenomegaly, and a white blood cell count of 38.3 ϫ 10 9 /L with 84% lymphocytes.…”

Section: Patient Materialsmentioning

confidence: 74%

The BCL11 gene family: involvement of BCL11A in lymphoid malignancies

Satterwhite

Sawada

Willis

et al. 2001

Blood

280

286

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region, is the pathologic target. However, by molecular cloning of t(2;14)(p13;q32.3) from 3 cases of aggressive B-cell chronic lymphocytic leukemia (CLL)/immunocytoma, this study has shown clustered breakpoints on chromosome 2p13 immediately upstream of a CpG island located about 300 kb telomeric of REL. This CpG island was associated with a Krü ppel zinc finger gene (BCL11A), which is normally expressed at high levels only in fetal brain and in germinal center B-cells. There were 3 major RNA isoforms of BCL11A, differing in the number of carboxy-terminal zinc fingers. All 3 RNA isoforms were deregulated as a consequence of t(2;14) (p13;q32.3). BCL11A was highly conserved, being 95% identical to mouse, chicken, and Xenopus homologues. BCL11A was also highly homologous to another gene ( IntroductionMany subtypes of malignancy are associated with specific chromosomal translocations, which play a pivotal role in the pathogenesis of disease. In the leukemias and lymphomas of mature B-cells, these frequently involve the immunoglobulin (IG) loci and result in deregulated expression of the translocated oncogene, due, in part, to the presence of potent B cell-specific transcriptional enhancers within the IG loci. 1 All the common IG translocations have been cloned. Paradigms include the deregulation of cyclin D1 by t(11;14)(q13;q32.3), found in all cases of mantle cell lymphoma; BCL2 by t(14;18)(q32.3;q21.3), found in 80% of follicular lymphoma; and MYC by t(8;14)(q24.1;q32.3) and variant translocations in all cases of Burkitt lymphoma. 1 On the basis of cytogenetics alone, several rare, but nonetheless recurrent IG translocations remain to be cloned, principally in aggressive large-cell B-NHL 2 ; their molecular cloning continues to allow the isolation of novel dominant oncogenes and to define new pathogenic mechanisms. 1,[3][4][5][6] Chromosomal translocation t(2;14) (p13;q32.3) is one example and has been reported in a variety of B-cell malignancies ranging from B-cell precursor acute lymphoblastic leukemia to myeloma. This translocation is frequently the sole cytogenetic abnormality within the neoplastic clone (Watson et al,7 Geisler et al, 8 Sonoki et al, 9 and http://cgap.nci.nih.gov/ Chromosomes/Mitelman). We report here the recurrent involvement and deregulated expression of a Krüppel zinc finger gene, BCL11A, in 4 cases of B-cell malignancy with t(2;14)(p13;q32.3). Patients, materials, and methods Patient materialFour patients with B-cell malignancies and t(2;14)(p13;q32) were studied. Patient material was studied after obtaining written informed consent and local ethical committee approval. Two unusual pediatric patients with CLL (referred to here as patients AS and LH) who exhibited this translocation have been reported on previously 10 ; the translocation breakpoints in these 2 cases were cloned using bacteriophage cloning. 11 In addition, 2 adult patients identified from our cytogenetic databases with identical translocations were also studied. Patient 3 was a previously well 62-year-old female who pres...

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Section: Patient Materialsmentioning

confidence: 74%

The BCL11 gene family: involvement of BCL11A in lymphoid malignancies

Satterwhite

Sawada

Willis

et al. 2001

Blood

280

286

View full text Add to dashboard Cite

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“…All of these features are not usually observed in proto-oncogenes and contrast with the fact that BCL-6 alteration is one of the most common abnormalities in NHL, also found in some lymphoma cases as the sole karyotypic abnormality. 62 BCL-6 protein is a transcriptional repressor acting with several partners [63][64][65] and controls expression of a wide spectrum of target genes, 68 but it can act also as a transcriptional activator under certain conditions. 66 For that reason, BCL-6 protein activity is related to the maturation stage of tumor cells and to expression of the protein partners, and most likely participates in a different way in FCL or DLBCL development.…”

Section: Discussionmentioning

confidence: 99%

Follicle center lymphoma is associated with significantly elevated levels of BCL-6 expression among lymphoma subtypes, independent of chromosome 3q27 rearrangements

Jardin¹,

Buchonnet²,

Parmentier

et al. 2002

Leukemia

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The BCL-6 gene, located on chromosome 3q27, is implicated in the normal germinal center formation and is frequently rearranged in a wide spectrum of lymphomas. However the links between genetic alterations and expression of the gene are not clearly determined. We established a quantitative RT-PCR assay based on TaqMan technology to quantify BCL-6 mRNA expression in different subtypes of lymphomas and to compare the level of expression in lymphomas characterized by the presence or absence of BCL-6 translocation. Total RNA was extracted from 105 nodes biopsies (35 diffuse large B cell lymphomas (DLBCL); 26 follicle center lymphomas (FCL); 7 marginal zone lymphomas (MZL); 6 mantle cell lymphomas (MCL); 6 chronic lymphocytic leukemia (CLL); 5 T cell lymphomas (TCL); 7 classical Hodgkin diseases (HD); 6 nodal metastasis (NM); and 7 reactive hyperplasia (RH)). BCL-6 gene rearrangement was assessed by Southern blot analysis in 75% of 3q27 + DLBCL (n = 20) cases and 67% of 3q27 + cases (n = 10). The highest level of relative BCL-6 expression was observed in FCL (9.12 ± 7.28) comparatively to the other lymphoma subtypes including DLBCL (2.53 ± 1.82; P Ͻ 0.001), MCL (1.23 ± 0.73), MZL (1.49 ± 1.3), HD (1.60 ± 1.00), TCL (1.75 ± 1.64), but also RH (3.91 ± 3.12) or NM (1.95 ± 2.6). Among the 26 FCL cases, we observed a lower expression in grade 3 (n = 8) than in grade 1/2 (P Ͻ 0.001). Conversely, we failed to show any difference between 3q27 + DLBCL and 3q27 − DLBCL cases (P = 0.42). Paradoxically BCL-6 expression in 3q27 + FCL (n = 10) was significantly lower than in 3q27 − FCL cases (P = 0.035). Finally, this study showed that BCL-6 expression in lymphoma is largely independent of chromosome 3q27 rearrangement and is more related to the histological subtype. Clinical implication and alternative deregulation pathways of BCL-6 expression remain to be determined.

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“…Furthermore, the breakpoint at 1q21 is frequently observed in diffuse large B-cell lymphomas (Cigudosa et al, 1999). The cells with the abnormality at the locus, which is important to lymphomagenesis, might grow up as the apparent malignant clones.…”

Section: Miwa Et Almentioning

confidence: 99%

Induction of Chromosomal Aberrations and Growth-Transformation of Lymphoblastoid Cell Lines by Inhibition of Reactive Oxygen Species-Induced Apoptosis with Interleukin-6

Miwa

Kanno

Munakata

et al. 2000

Laboratory Investigation

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SUMMARY:Etiological evidence, indicating the relationships between the onset of malignant lymphoma and pre-existing chronic inflammation, has been accumulated. For the autonomous growth of malignant tumor, genetic lesions, such as chromosomal aberrations, amplification of oncogenes, and mutations of genes involved in the cell cycle regulation, must be essential. However, how the inflammation promotes the accumulation of genetic lesions and induces the autonomous growth of lymphoid cells remains unclear. Reactive oxygen species released by polymorphonuclear leukocytes and macrophages are factors causing DNA damage in the foci of inflammation, and thus could play a role in lymphomagenesis. The xanthine/xanthine oxidase (X/XOD) system produces a mixture of hydrogen peroxide and superoxide anion extracellularly, and thus serves as an in vitro source of reactive oxygen species. Cell death of lymphoblastoid cell lines (LCLs) was induced with X/XOD treatment in a dose-dependent manner. DNA fragmentation, which is the characteristic feature of apoptosis, was observed in LCLs at 4 -8 hours after X/XOD treatment. Among cytokines such as interleukin-6 (IL-6), IL-10, and interferon-␥, only pretreatment with IL-6 gave LCLs the resistance to X/XOD-induced cell death in a dose-dependent manner. The proportion of apoptotic cells in X/XOD-treated LCL culture was decreased with IL-6 pretreatment by quantification with flow cytometric analysis. Treatment of LCLs with IL-6 for 48 hours up-regulated bcl-2 mRNA expression. Furthermore, the LCLs repeatedly treated with X/XOD and cultured with or without IL-6 showed many more structural abnormalities of chromosomes than those without X/XOD treatment. Colony forming efficiency of X/XOD-treated LCLs with IL-6 was significantly higher than those without IL-6, and even relatively higher than LCLs without X/XOD treatment. IL-6 could support the survival of non-neoplastic B cells and accelerate the malignant transformation of B lineage cells in inflammatory lesions. (Lab Invest 2000, 80:725-734).

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Cytogenetic analysis of 363 consecutively ascertained diffuse large B-cell lymphomas

Cited by 155 publications

References 57 publications

The BCL11 gene family: involvement of BCL11A in lymphoid malignancies

The BCL11 gene family: involvement of BCL11A in lymphoid malignancies

Follicle center lymphoma is associated with significantly elevated levels of BCL-6 expression among lymphoma subtypes, independent of chromosome 3q27 rearrangements

Induction of Chromosomal Aberrations and Growth-Transformation of Lymphoblastoid Cell Lines by Inhibition of Reactive Oxygen Species-Induced Apoptosis with Interleukin-6

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