Advances in the biology and therapy of diffuse large B-cell lymphoma: moving toward a molecularly targeted approach

Abramson, Jeremy S.; Shipp, Margaret A.

doi:10.1182/blood-2005-02-0687

Cited by 185 publications

(159 citation statements)

References 95 publications

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“…Rituximab is a monoclonal antibody that binds the B-cell transmembrane protein CD20 resulting in lymphoma cell lysis. It started to be used in Europe in 2000, but not simultaneously in all countries [36][37][38] and significant survival improvements for DLBCL and FL patients treated with rituximab have been described in a population-based study. 39,40 The treatment of multiple myeloma has also changed over the last decade with the introduction of thalidomide, lenalidomide and proteasome inhibitors (bortezomib), as add-on therapy to conventional cytotoxic and transplantation regimens.…”

Section: Discussionmentioning

confidence: 99%

Survival of European patients diagnosed with lymphoid neoplasms in 2000-2002: results of the HAEMACARE project

Marcos‐Gragera¹,

Allemani²,

Ţereanu³

et al. 2011

Haematologica

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The European Cancer Registry-based project on hematologic malignancies (HAEMACARE), set up to improve the availability and standardization of data on hematologic malignancies in Europe, used the European Cancer Registry-based project on survival and care of cancer patients (EUROCARE-4) database to produce a new grouping of hematologic neoplasms (defined by the International Classification of Diseases for Oncology, Third Edition and the 2001/2008 World Health Organization classifications) for epidemiological and public health purposes. We analyzed survival for lymphoid neoplasms in Europe by disease group, comparing survival between different European regions by age and sex

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Section: Discussionmentioning

confidence: 99%

Survival of European patients diagnosed with lymphoid neoplasms in 2000-2002: results of the HAEMACARE project

Marcos‐Gragera¹,

Allemani²,

Ţereanu³

et al. 2011

Haematologica

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“…About 30-40% of patients can be cured using a combined chemotherapeutic regimen of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). Addition of rituximab, an anti-CD20 monoclonal antibody, has significantly improved the cure rate to B60% in large clinical trials, 4,5 and rituximab in combination with CHOP was recently approved by food and drug administration (FDA) as the first-line treatment for DLBCL. Despite this advance, as well as other limited options, 30-40% of patients still succumb to their disease.…”

Section: Introductionmentioning

confidence: 99%

Tyrosine kinase inhibition in diffuse large B-cell lymphoma: molecular basis for antitumor activity and drug resistance of dasatinib

et al. 2008

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Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Although some patients can be cured by current therapies, novel agents are needed to further improve outcomes. We hypothesized that Src tyrosine kinase inhibition by dasatinib may have antilymphoma effects. Here, we demonstrate that dasatinib inhibits cell growth through G 1 -S blockage in five of seven DLBCL cell lines at clinically achievable concentrations. Compared to resting B cells, DLBCL has increased tyrosine phosphorylation activities. As expected, dasatinib inhibits phosphorylation of several Src family kinase members. However, this inhibition occurs in all cell lines regardless of their proliferative response to the drug. In contrast, the activity of two downstream signaling molecules, Syk and phospholipase Cc2 (PLCc2), are well correlated with cell line sensitivity to dasatinib, suggesting that these molecules are crucial in mediating the proliferation of activated lymphoma cells. Furthermore, dasatinib inhibits B-cell receptor signaling in primary lymphoma cells. Together, our findings not only show dasatinib as a potentially useful therapy for DLBCL but also provide insights into the pathogenesis of the lymphoma. The results further suggest the possibility of using Syk and PLCc2 as biomarkers to predict dasatinib therapeutic response in prospective clinical trials.

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“…4,5 More recently, the existence of a gray zone between diffuse large B-cell lymphoma and Hodgkin lymphoma has been proposed. 33 Since mediastinal large B-cell lymphoma and T-cell/histocyte-rich B-cell lymphoma share characteristics of Hodgkin lymphoma and diffuse large B-cell lymphoma, they are considered gray zone lymphomas. 15,33 It is noteworthy that TIMP-1 expression is frequently seen in large anaplastic or multinucleate bizarre tumor cells, and has been shown to be closely related to the activation of STAT3 signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

“…33 Since mediastinal large B-cell lymphoma and T-cell/histocyte-rich B-cell lymphoma share characteristics of Hodgkin lymphoma and diffuse large B-cell lymphoma, they are considered gray zone lymphomas. 15,33 It is noteworthy that TIMP-1 expression is frequently seen in large anaplastic or multinucleate bizarre tumor cells, and has been shown to be closely related to the activation of STAT3 signaling pathway. Thus, although TIMP-1( þ ) diffuse large B-cell lymphoma remains to be further defined, it is speculated that it might represent a gray zone lymphoma between diffuse large B-cell lymphoma and Hodgkin lymphoma, or an anaplastic variant of diffuse large B-cell lymphoma.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathologic implications of tissue inhibitor of metalloproteinase-1-positive diffuse large B-cell lymphoma

Choi

Lee

et al. 2006

Modern Pathology

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The tissue inhibitor of metalloproteinase-1 (TIMP-1) is a stromal factor that promotes plasmablastic differentiation, and the survival of germinal center B-cells. The expression of TIMP-1 is known to be correlated with a subset of non-Hodgkin lymphoma at the mRNA level, and Epstein-Barr virus infection in vitro. To characterize TIMP-1( þ ) diffuse large B-cell lymphoma, TIMP-1 expression was investigated in tissue microarrays from 182 cases of de novo diffuse large B-cell lymphoma and compared with prognostic factors, immunophenotypes, and Epstein-Barr virus infection status. TIMP-1 was expressed not only in tumor cells themselves, in 14 of 182 cases (8%), designated as TIMP-1( þ ) diffuse large B-cell lymphoma, but also in stromal cells like fibroblasts and endothelial cells. In univariate analysis and hierarchical clustering, our findings suggest that TIMP-1 expression may represent a distinct subgroup. In multivariate analysis, TIMP-1( þ ) diffuse large B-cell lymphoma (n ¼ 14) was associated with unfavorable outcomes compared to TIMP-1(À) diffuse large B-cell lymphoma (n ¼ 168) (odds ratio ¼ 2.5, P ¼ 0.049). Together with TIMP-1 expression, age (greater than 60 years), the presence of B-symptoms, abnormal lactate dehydrogenase level, or more advanced stage (III/IV) was correlated with a poor overall survival. However, TIMP-1 expression in diffuse large B-cell lymphoma was not correlated with other prognostic factors including: clinical stage, international prognostic index score, and nongerminal center B-cell phenotype, as well as Epstein-Barr virus infection. Our results suggest that TIMP-1 expression may be an independent negative prognostic factor in patients with diffuse large B-cell lymphoma.

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Advances in the biology and therapy of diffuse large B-cell lymphoma: moving toward a molecularly targeted approach

Cited by 185 publications

References 95 publications

Survival of European patients diagnosed with lymphoid neoplasms in 2000-2002: results of the HAEMACARE project

Survival of European patients diagnosed with lymphoid neoplasms in 2000-2002: results of the HAEMACARE project

Tyrosine kinase inhibition in diffuse large B-cell lymphoma: molecular basis for antitumor activity and drug resistance of dasatinib

Clinicopathologic implications of tissue inhibitor of metalloproteinase-1-positive diffuse large B-cell lymphoma

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