Bone marrow histological patterns can predict survival of patients with grade 1 or 2 follicular lymphoma: a study from the Groupe d‘Etude des Lymphomes Folliculaires

Canioni, Danielle; Brice, Pauline; Lepage, Éric; Chababi, Myrna; Meignin, Véronique; Salles, Bruno César Corrêa; Xerri, Luc; Peaud, Pierre-Yves; Rousselot, Philippe; Peuchmaur, Michel; Solal‐Céligny, Philippe; Brousse, Nicole

doi:10.1111/j.1365-2141.2004.05046.x

Cited by 30 publications

(17 citation statements)

References 26 publications

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“…BM involvement is mostly associated with paratrabecular aggregates composed of centrocytes expressing different FL-specific antigens, including CD10, bcl-2 and bcl-6. 10,11,18 According to previous reports, growth pattern, immunophenotype and the ongoing hypermutation activity of the original neoplastic clone are retained during the expansion of neoplastic cells to adjacent GCs and distant lymph nodes (LN). 5,14,15 However, details of tumor cell dissemination to the BM have remained largely unknown, and the biological characteristics of the tumor clone responsible for BM infiltration have not been studied.…”

Section: Introductionmentioning

confidence: 99%

Clonal selection in the bone marrow involvement of follicular lymphoma

et al. 2005

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To characterize the pathways of bone marrow (BM) involvement of follicular lymphoma (FL), we performed morphological and immunophenotypical analysis of tumor cells from lymph nodes (LNs) and corresponding BMs in 21 patients with FL. In three cases, genealogical trees were constructed based on the immunoglobulin variable region heavy chain (IgV H ) gene sequences of tumor clones from LNs and BMs. Results showed that FLs within the BMs display identical or lower cytological grades than in the LNs. In the majority of cases, different proportions of tumor cells expressed bcl-2, CD10 and Ki67 in LNs and BMs. Tumor cells in the BM showed ongoing somatic hypermutation of the IgV H genes; the distribution of these mutations was highly consistent with antigen selection. The topology of the genealogical trees revealed that different subclones populate the LN and BM and BM infiltration may occur at different points of the clonal evolution of FL. Early descendants of the original tumor clone and derivatives of diversified tumor clones may invade the BM. These results suggest that the BM involvement of FL is associated with intensive clonal selection of tumor cells, and the BM provides a microenvironment similar to the germinal centers of LNs, where tumor cells retain their biological nature.

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Section: Introductionmentioning

confidence: 99%

Clonal selection in the bone marrow involvement of follicular lymphoma

et al. 2005

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“…Bone marrow (BM) involvement is found in up to 70% of FL cases at diagnosis. 25 This infiltration is associated with the emergence of ectopic LN-like reticular cells, few of them expressing the FDC-associated markers CD21 and CD35. 26 BM provides thus a preferred stromal microenvironment for FL cell growth.…”

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confidence: 99%

Human mesenchymal stem cells isolated from bone marrow and lymphoid organs support tumor B-cell growth: role of stromal cells in follicular lymphoma pathogenesis

Amé-Thomas¹,

Hajjami²,

Monvoisin³

et al. 2006

Blood

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IntroductionSeveral subsets of stromal cells, in particular follicular dendritic cells (FDCs) and fibroblastic reticular cells (FRCs), are found within secondary lymphoid organs where they play a key role in the initiation and maintenance of efficient immune responses. FDCs are restricted to germinal centers (GCs) and allow B-cell migration, selection, and differentiation through a complex set of survival factors including BCR-mediated signal, chemokines, cytokines, and adhesion molecules. 1 B-cell selection relies on an affinitybased competition for the fixation of antigen, presented as immune complexes by CD21 hi CD35 hi FDCs. Only B cells with high-affinity BCR receive survival signals from FDCs, capture antigen, and present it to CD4 ϩ T cells that deliver additional survival and maturation signals. 2,3 Conversely, FRCs are less well characterized. They are tightly interconnected in the paracortex of lymph nodes (LNs) where they secrete and ensheath various extracellular matrix components, thus building an intricate network of conduits, connecting afferent lymphatic vessels to high endothelial venules (HEVs). 4 This conduit system allows the rapid transport of soluble antigens from the periphery to the resident myeloid immature dendritic cells (DCs). 5 In addition, part of this reticular network called cortical ridge favors B, T, and DC recruitment and reciprocal interactions, in particular through the production of constitutive and inflammatory chemokines. 6,7 CCL19, CCL21, and CXCL12 are involved in the migration of mature myeloid DCs and naive B and T cells, whereas CXCL9, CXCL10, and CCL5 are crucial for the migration of activated T cells and plasmacytoid DCs. [8][9][10] Strikingly, CCL19 and CCL21 are not synthesized by human HEVs but rather by stromal cells in the T-cell zone. 11,12 These chemokines further reach luminal surface of HEVs by endothelial uptake and transcytosis. FRCs provide therefore a favorable and highly specialized lymphoid environment for immune cell migration and activation.The ontogeny of FRCs and FDCs remains unclear, but these cells are supposed to be of mesenchymal origin. LN organogenesis in the mouse relies on the interaction between CD45 Ϫ VCAM-1 ϩ ICAM-1 ϩ mesenchymal cells and CD45 ϩ CD4 ϩ CD3 Ϫ lymphoid tissue inducer cells in the LN anlagen. 13 A prominent role is attributed to lymphotoxin-␤ receptor (LT␤R) triggering by membrane-bound LT␣1␤2 (LT) and to tumor necrosis factor receptor 1 (TNFR1)/tumor necrosis factor-␣ (TNF). 14,15 Adult lymphoid tissues are highly dynamic structures that retain several features of embryonic organization. 16 Functional mouse FRCs able to construct a reticular meshwork and to secrete inflammatory chemokines could be generated in vitro by stimulation of LN-derived stromal cell lines using a combination of TNF and LT. 17 In vivo, transgenic expression of LT or injection of newborn LN-derived The online version of this article contains a data supplement.The publication costs of this article were defrayed in part by page charge payment. Therefo...

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“…Collectively, these data suggest that MSCs and their medullar and SLO-related progeny could variably modulate normal and lymphoma B-cell survival and growth, depending on the environmental context. This could be of particular importance in follicular lymphoma (FL), the most frequent indolent non-Hodkgin's lymphoma, which is generally a disseminated disease with initial involvement of lymph nodes and bone marrow (24,25). IFN-g and TNF have been detected in FL-invaded lymph nodes using in situ hybridization or PCR experiments (26,27), but the reciprocal role of these two cytokines on the bidirectional crosstalk between malignant cells and their stromal microenvironment has not been considered.…”

Section: Introductionmentioning

confidence: 99%

Functional Alteration of the Lymphoma Stromal Cell Niche by the Cytokine Context: Role of Indoleamine-2,3 Dioxygenase

et al. 2009

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Human mesenchymal stem cells (MSC) strongly repress activated T-cell proliferation through the production of a complex set of soluble factors, including the tryptophancatabolizing enzyme indoleamine 2,3-dioxygenase (IDO), which is induced by IFN-;. Conversely, MSCs support survival of follicular lymphoma (FL) B cells, in particular after exposure to tumor necrosis factor-A (TNF) and lymphotoxin-A1B2 (LT). The role of MSCs on normal and malignant B-cell growth in steady-state and inflammatory conditions remains to be fully explored. We show here that resting MSCs sustain activated normal B-cell proliferation and survival, whereas IFN-;-conditioned MSCs mediate IDOdependent B-cell growth arrest and apoptosis. IFN-;, TNF, and LT are significantly overexpressed by the microenvironment of invaded FL-lymph nodes, but their relative expression patterns are highly heterogeneous between samples. In vitro, IFN-; abrogates the B-cell supportive phenotype induced by TNF and LT on MSCs. Moreover, IFN-; overrules the growth promoting effect of MSCs on primary purified FL B cells. Altogether, these results underline the crucial role of the cytokine context in the local crosstalk between malignant cells and their microenvironment and provide new insights into our knowledge of the FL cell niche that emerges as a new promising target for innovative therapeutic strategies. [Cancer Res 2009;69(7):3228-37]

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Bone marrow histological patterns can predict survival of patients with grade 1 or 2 follicular lymphoma: a study from the Groupe d‘Etude des Lymphomes Folliculaires

Cited by 30 publications

References 26 publications

Clonal selection in the bone marrow involvement of follicular lymphoma

Clonal selection in the bone marrow involvement of follicular lymphoma

Human mesenchymal stem cells isolated from bone marrow and lymphoid organs support tumor B-cell growth: role of stromal cells in follicular lymphoma pathogenesis

Functional Alteration of the Lymphoma Stromal Cell Niche by the Cytokine Context: Role of Indoleamine-2,3 Dioxygenase

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