Bcl-2 reduces lymphomagenesis in ΔV-TCRβ transgenic mice

Acton, D; Jacobs, Heinz; Domen, Jos; Berns, Anton

doi:10.1038/sj.onc.1201089

Cited by 9 publications

(2 citation statements)

References 18 publications

(30 reference statements)

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“…The overexpression of Bcl-2 as a transgene, even in the early stages of T-cell development where leukemogenesis is more likely to occur, does not cause the accumulation of pro-T cells and no T-cell leukemia was reported to arise in Bcl-2 transgenic mice (39)(40)(41). Some reports even indicate that overexpression of Bcl-2 as a transgene may actually reduce the incidence of T-cell lymphomagenesis (42).…”

Section: Discussionmentioning

confidence: 99%

Bcl-2 Overexpression Enhances Tumor-Specific T-Cell Survival

et al. 2005

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Although immunotherapy based on the adoptive transfer of tumor-specific T lymphocytes has been shown to result in dramatic clinical responses in some patients, the relatively low levels of engraftment and persistence of the adoptively transferred cells may limit these responses in many patients. In an attempt to develop strategies for prolonging the survival of adoptively transferred T cells, we have carried out studies in which T cells obtained from healthy donors as well as tumor-specific T cells were transduced with a retrovirus expressing the human Bcl-2 gene. Our results indicate that these transduced T cells overexpress Bcl-2, are resistant to death, and have a survival advantage following interleukin-2 withdrawal compared with control T cells transduced with a retrovirus expressing green fluorescent protein. Tumor-specific T cells overexpressing Bcl-2 maintained their ability to specifically recognize and respond to target cells. Furthermore, we show that adoptive immunotherapy of an established B16 tumor can be significantly enhanced by overexpressing Bcl-2 in melanoma-specific T-cell receptor transgenic T cells. Our data suggest that adoptive immunotherapy approaches to the treatment of cancer patients may be enhanced using Bcl-2-modified tumorreactive T cells. (Cancer Res 2005; 65(5): 2001-8)

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Section: Discussionmentioning

confidence: 99%

Bcl-2 Overexpression Enhances Tumor-Specific T-Cell Survival

et al. 2005

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“…105 Tumors develop from double-positive T cells at a high incidence, and unexpectedly, enforced expression of the Bcl2 oncogene reduces lymphomagenesis. 106 It should be noted, however, that, although a V-less T-cell receptor-␤ can be produced by retroviral insertional mutagenesis in cat and in mouse lymphomas, 107,108 it has not been associated with a human disease.…”

Section: Constitutive Activation Of Antigen Receptors and Animal Modelsmentioning

confidence: 99%

B-cell receptors and heavy chain diseases: guilty by association?

Corcos

Osborn

Matheson

2011

Blood

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IntroductionImmunoglobulin (Ig), as paired heavy chain (HC) and light chain (LC), occurs in a secreted form as antibody. It also exists in a membrane form (HC ϩ LC) sheathed by the Ig␣/Ig␤ heterodimer 1,2 forming the B-cell receptor (BCR). Here it plays a major role in B lymphocyte activation 3 and survival. 4,5 Heavy chain diseases (HCDs) are rare B-cell proliferative disorders characterized by the presence in the serum of monoclonal, incomplete, Ig HCs not associated with LCs. 6 Alterations in the Ig HC gene leading to HC molecules have been identified in HCD, with deletions in the variable (V) domain in all but one case studied to date. 7 This makes the HC gene mutation a recurrent alteration in a tumor, which tends to suggest a role in pathogenesis. Whereas much attention has been paid to the secreted form of the Ig in these diseases, it now appears that the membrane form of the truncated HC, as part of the BCR, has abnormal aggregation and signaling properties that may contribute to disease development. Here we review the current knowledge on the functions of surface HC and on the alterations of these proteins in HCD. HCD definitionThe definition of HCD is usually a biochemical one: 8 the presence of an abnormal HC not associated with LC in the serum. However, this biochemical definition has 2 caveats: (1) there are lymphoproliferations where abnormal HCs are not secreted, although produced; 9 and (2) a biochemical alteration is not a disease by itself. In this review, we focus on HC protein alterations associated with lymphomas, whether they meet the traditional biochemical criteria or not. Clinical features and classificationThe clinical aspects of HCD have been recently reviewed elsewhere 10 and are summarized here. ␣-HCD, 11 the most common HCD with more than 400 reported cases, 12 is almost equivalent to immunoproliferative small intestinal disease (IPSID), 13 although there are gastric and pulmonary forms of ␣-HCD, and IPSID can also be associated with ␥-HCD. IPSID, a variant of extranodal marginal zone lymphoma, is characterized by the presence of diffuse mucosal infiltrates, 14 involving a large part of the intestine, thus producing malabsorption. 15 It affects mainly younger adults in the Middle East and the Mediterranean region. Treatment of IPSID at an early phase with antibiotics causes remission in some patients, 16 which may be the result of their effects on Campilobacter jejuni, a bacterium strongly associated with IPSID. 17 ␥-HCD is a heterogeneous condition but usually presents as an aggressive form of lymphoplasmacytic lymphoma, whereas -HCD, the rarest form of HCD, typically presents as a chronic lymphocytic leukemia, frequently with vacuoles in the malignant lymphocytes, and the presence of light chains in the urine. 10 It is of interest to note that all of these B-cell proliferations, even if they have a large plasma cell component, are lymphomas rather than plasma cell proliferations. The latter are known not to require an HC for survival. 18 Functions of surface (or membrane) HCsAll...

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