Angiogenesis in Non-Hodgkin's Lymphoma: An Intercategory Comparison of Microvessel Density

Aggarwal, Divya; Srivastava, Gunjan; Gupta, Ruchika; Pant, Leela; Krishan, Gopal; Singh, Sompal

doi:10.5402/2012/943089

Cited by 16 publications

(27 citation statements)

References 17 publications

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“…2C). As this has been reported for solid tumors and certain non-Hodgkin's lymphomas, including T cell lymphoma (22, 23), we asked if this was associated with increased expression of pro-angiogenic factors such as VEGF. Indeed, VEGF mRNA levels were significantly enhanced in Rpl22 −/− lymphomas (Fig.…”

Section: Resultsmentioning

confidence: 92%

Ribosomal Protein Rpl22 Controls the Dissemination of T-cell Lymphoma

et al. 2016

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Mutations in ribosomal proteins cause bone marrow failure syndromes associated with increased cancer risk, but the basis by which they do so remains unclear. We reported previously that the ribosomal protein Rpl22 is a tumor suppressor in T cell acute lymphoblastic leukemia/lymphoma (T-ALL), and that loss of just one Rpl22 allele accelerates T-cell lymphomagenesis by activating NF-κB and inducing the stem cell factor Lin28B. Here, we show that, paradoxically, loss of both alleles of Rpl22 restricts lymphoma progression through a distinct effect on migration of malignant cells out of the thymus. Lymphoma-prone AKT2-transgenic or PTEN-deficient mice on an Rpl22−/− background developed significantly larger and markedly more vascularized thymic tumors than those observed in Rpl22+/+ control mice. But, unlike Rpl22+/+ or Rpl22+/− tumors, Rpl22−/− lymphomas did not disseminate to the periphery and were retained in the thymus. We traced the defect in the Rpl22−/− lymphoma migratory capacity to downregulation of the KLF2 transcription factor and its targets, including the key migratory factor sphingosine 1-phosphate receptor 1 (S1PR1). Indeed, re-expression of the S1PR1 in Rpl22-deficient tumor cells restores their migratory capacity in vitro. The regulation of KLF2 and S1PR1 by Rpl22 appears to be proximal as Rpl22 re-expression in Rpl22-deficient lymphoma cells restores expression of KLF2 and S1P1R, while Rpl22 knockdown in Rpl22-sufficient lymphomas attenuates their expression. Collectively, these data reveal that, while loss of one copy of Rpl22 promotes lymphomagenesis and disseminated disease, loss of both copies impairs responsiveness to migratory cues and restricts malignant cells to the thymus.

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Section: Resultsmentioning

confidence: 92%

Ribosomal Protein Rpl22 Controls the Dissemination of T-cell Lymphoma

et al. 2016

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“…Positive association between MVD and patient outcome is in contrast with the notion that in hematologic malignancies, as well as in solid tumors the increase of angiogenesis-associated variables is related to adverse prognosis 15,22,28 . Aggarwal et al 20 found higher MVD in aggressive lymphoma such as peripheral T- cell lymphoma and DLBCL, and low MVD in lowgrade lymphomas 2 .…”

Section: Discussionmentioning

confidence: 98%

“…Angiogenesis is a multistep process playing a crucial role in the progression and metastasis of various tumors, including those of visceral organs and hematolymphoid malignancies 20 . Tumor angiogenesis has been well documented both in experimental and clinical studies, and the degree of angiogenesis was closely associated with tumor progression and shorter patient survival in many types of cancer 21,22 .…”

Section: Discussionmentioning

confidence: 99%

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Clinical Significance of VEGF-A and Microvessel Density in Diffuse Large B-Cell Lymphoma and Low-Grade Follicular Lymphoma

Shahini

Gašparov

Petruševska

et al. 2017

ACC

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Angiogenesis is essential for the development, growth and progression of tumors. Although vascular endothelial growth factor (VEGF) is a well-known proangiogenic factor, its impact on lymphoma has not yet been fully clarified. The aim of this study was to evaluate VEGF-A -expression and microvessel density (MVD) in aggressive lymphoma such as diffuse large B-cell lymphoma (DLBCL), in indolent lymphomas such as low-grade follicular lymphoma (FL), and in lymph node reactive follicular hyperplasia (FH). In 80 prospective and retrospective cases (30 DLBCL, 30 FL and 20 FH), CD31 was analyzed by immunohistochemical staining assessing density of blood vessels, as well as the total number of CD31 positive endothelial cells. The results were compared with relevant clinical data. MVD was 85% in FH, followed by 60% in DLBCL and 43% in low-grade FL. VEGF-A was significantly higher in DLBCL than in low-grade FL and FH. A statistically significant association of MVD and VEGF-A with the International Prognostic Index (IPI) was found in DLBCL. High MVD and VEGF-A expression was observed in DLBCL patients with high IPI, while there was no statistically significant association between MVD and VEGF-A with the Follicular Lymphoma International Prognostic Index in low-grade FL. Our results suggested an important relationship between angiogenesis and high-grade lymphoma.

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“…Протокол включает два курса R-DHAP: дексаметазон по 40 мг внутривенно в 1-4-й день курса, цитарабин в высоких дозах (НD-Ara-C) 2000 мг/м 2 внутривенно во 2-й день, цисплатин 100 мг/м 2 внутривенно в 1-й день. Применение препаратов платины обеспечивает блокирование ряда механизмов лекарственной устойчивости, поэтому платиносодержащие курсы широко используются в качестве ХТ лимфом второй линии [18,19]. Два курса R-DHAP позволяют оценить химиочувствительность опухоли, которая является важным прогнозирующим фактором, а также дает возможность значительно сократить объем опухолевой массы [20].…”

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