Molecular histogenesis of posttransplantation lymphoproliferative disorders

Capello, Daniela; Cerri, Michaela; Muti, Giuliana; Berra, Eva; Oreste, Pierluigi; Deambrogi, Clara; Rossi, Davide; Dotti, Giampietro; Conconi, Annarita; Viganò, Mario; Magrini, Umberto; Ippoliti, G; Morra, Enrica; Gloghini, Annunziata; Rambaldi, Alessandro; Paulli, Marco; Carbone, Antonino; Gaïdano, Gianluca

doi:10.1182/blood-2003-05-1683

Cited by 103 publications

(107 citation statements)

References 44 publications

(83 reference statements)

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“…8,[18][19][20][21] For IgV sequencing, a DNA direct sequencing approach was utilized in all cases. 21 Sequences were analyzed as reported 21 and considered mutated if deviation from the closest germline gene was X2%. Criteria for D element identification in CDR3 were as reported.…”

Section: Analysis Of V H and V L Genesmentioning

confidence: 99%

Evidence of biased immunoglobulin variable gene usage in highly stable B-cell chronic lymphocytic leukemia

et al. 2004

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Recognition of biased immunoglobulin variable (IgV) gene usage in B-cell chronic lymphocytic leukemia (B-CLL) may yield insight into leukemogenesis and may help to refine prognostic categories. We explored Ig variable heavy (V H ) and light (V L ) chain gene usage in highly stable and indolent B-CLL (n ¼ 25) who never required treatment over 10 or more years. We observed an unexpectedly high usage of mutated V H 3-72 (6/25; 24.0%), a gene that was otherwise rare in B-CLL (7/805; 0.87%; Po0.01), including mutated cases (6/432; 1.39%; Po0.01) and was exceptional among indolent (1/230, 0.435%; Po0.01), and aggressive B-cell lymphomas (0/105; Po0.01). Three of six V H 3-72 B-CLL cases utilized the same V L V j 4-1 gene. Two V H 3-72 B-CLL cases had highly homologous V H complementarity determining regions 3 (CDR3s), encoding Cys-XXXX-Cys domains, and utilized V j 4-1 genes with homologous IgV L CDR3s. An identical threonine to isoleucine change at codon 84 of V H 3-72 framework region 3 (FR3) recurred in four cases of highly stable V H 3-72 B-CLL. This mutation is expected to cause a conformational change of FR3 proximal to CDR3 that might critically affect high-affinity antigen binding. B-cell receptors encoded by V H 3-72 may identify a specific B-CLL group and be implicated in leukemogenesis through an antigen-driven expansion of B cells.

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Section: Analysis Of V H and V L Genesmentioning

confidence: 99%

Evidence of biased immunoglobulin variable gene usage in highly stable B-cell chronic lymphocytic leukemia

et al. 2004

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“…9 The molecular histogenesis in these cases is heterogeneous, although CD138 þ cases have been well documented. 10 It is possible that CD20 negativity may account for some instances of lack of response to rituximab.…”

mentioning

confidence: 99%

Epstein–Barr virus-associated, CD20− polyclonal lymphoproliferative disorder after matched unrelated donor marrow transplantation

Anderlini

Valbuena

Champlin

et al. 2004

Bone Marrow Transplant

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“…The latent gene expression seen in the EBVcarrying tumors varies according to the tissue origin of the tumors and activation/differentiation stage of the malignant cells (3). The EBV-positive Burkitt lymphoma (BL), primary effusion lymphomas, and some nasopharyngeal carcinomas (NPC) express only the EBNA-1 protein (type I latency), whereas classical Hodgkin lymphomas (cHL) (4), a part of NPCs (5), nasal NK/T lymphomas (6), peripheral T cell lymphomas (7), some diffuse large B cell lymphomas (8) and posttransplant lymphomas (PTLDs) (9,10), and EBV-positive B cells in angioimmunoblastic T cell lymphomas (11) express EBNA-1, LMP-1, and LMP-2 (type II latency) (1,3).…”

mentioning

confidence: 99%

IL-21 imposes a type II EBV gene expression on type III and type I B cells by the repression of C- and activation of LMP-1-promoter

Kis

Salamon

Persson

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Epstein-Barr virus (EBV) is associated with a variety of human tumors. Although the EBV-infected normal B cells in vitro and the EBV-carrying B cell lymphomas in immunodeficient patients express the full set of latent proteins (type III latency), the majority of EBVassociated malignancies express the restricted type I (EBNA-1 only) or type II (EBNA-1 and LMPs) viral program. The mechanisms responsible for these different latent viral gene expression patterns are only partially known. IL-21 is a potent B cell activator and plasma cell differentiation-inducer cytokine produced by CD4 + T cells. We studied its effect on EBV-carrying B cells. In type I Burkitt lymphoma (BL) cell lines and in the conditional lymphoblastoid cell line (LCL) ER/ EB2-5, IL-21 potently activated STAT3 and induced the expression of LMP-1, but not EBNA-2. The IL-21-treated type I Jijoye M13 BL line ceased to proliferate, and this was paralleled by the induction of IRF4 and the down-regulation of BCL6 expression. In the type III LCLs and BL lines, IL-21 repressed the C-promoter-derived and LMP-2A mRNAs, whereas it up-regulated the expression of LMP-1 mRNAs. The IL-21-treated type III cells underwent plasma cell differentiation with the induction of Blimp-1, and high levels of Ig and Oct-2. IL-21 might be involved in the EBNA-2-independent expression of LMP-1 in EBV-carrying type II cells. In light of the fact that IL-21 is already in clinical trials for the treatment of multiple malignancies, the in vivo modulation of EBV gene expression by IL-21 might have therapeutic benefits for the EBV-carrying malignancies.Epstein-Barr virus | IL-21 | lymphoma | STAT3

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Molecular histogenesis of posttransplantation lymphoproliferative disorders

Cited by 103 publications

References 44 publications

Evidence of biased immunoglobulin variable gene usage in highly stable B-cell chronic lymphocytic leukemia

Evidence of biased immunoglobulin variable gene usage in highly stable B-cell chronic lymphocytic leukemia

Epstein–Barr virus-associated, CD20− polyclonal lymphoproliferative disorder after matched unrelated donor marrow transplantation

IL-21 imposes a type II EBV gene expression on type III and type I B cells by the repression of C- and activation of LMP-1-promoter

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