RANKL expression in a case of follicular lymphoma

Barcala, Virna; Ruybal, Paula; Rivello, Hernán García; Waldner, Claudia; Ascione, Amanda; Mongini, C.

doi:10.1034/j.1600-0609.2003.00067.x

Cited by 8 publications

(7 citation statements)

References 6 publications

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“…In MM, the production of osteoclast-activating factors such as RANKL and IL-6 is considered to be one of the mechanisms which results in the development of bone lesions and hypercalcemia [5]. Excessive expression of RANKL was also reported in lymphoma [12], adult T cell leukemia [13], and chronic lymphocytic leukemia [14]. In IgG4RD, there are a number of reports which described an elevation of serum IL-6 [15][16][17].…”

Section: Discussionmentioning

confidence: 99%

A case of fatal osteolytic hypercalcemia complicated with IgG4-related ophthalmic disease leading to renal failure

et al. 2018

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A 40-year-old male was hospitalized with renal impairment and severe hypercalcemia. His concentration of serum IgG4 was high, but serum whole PTH, 1-25(OH) vitamin D3 and PTHrP were not elevated. Computed tomography showed swelling of the bilateral lacrimal glands and systemic lymphadenopathy. The histological findings of lacrimal gland biopsy fulfilled the diagnostic criteria of IgG4-related ophthalmic disease (IgG4ROD). Bone scintigraphy showed increased ectopic uptake in the stomach, heart, lungs, and kidneys. He died on day 16 of admission, although the therapies for hypercalcemia were continued. Autopsy results showed an increase of osteoclasts in the bone marrow and metastatic calcification in multiple organs, and excluded from the differential diagnosis other disorders which present lymph-node swelling and hypercalcemia such as cancer, lymphoma, Castleman's disease, and sarcoidosis. He was given a diagnosis of IgG4ROD with osteolytic hypercalcemia.

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Section: Discussionmentioning

confidence: 99%

A case of fatal osteolytic hypercalcemia complicated with IgG4-related ophthalmic disease leading to renal failure

et al. 2018

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“…Regarding the mechanisms underlying this interaction, several studies already documented an aberrant RANKL expression in different B cell malignancies such as CLL, multiple myeloma and follicular lymphoma 13 – 21 . Actually, Secchiero et al .…”

Section: Discussionmentioning

confidence: 99%

“…Factors triggering this progression are still not fully clarified and no treatment has shown capability to halt disease progression in the asymptomatic phase 11 , 12 . However, there is accumulating evidence that the TNF superfamily member Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) and its receptor RANK do play a role in CLL clone upkeep and in the progression of other B-cell related hematologic malignancies 13 – 18 . This pathway is indeed crucial in the immune system’s physiological development, as mice lacking RANK show absent lymph node development and impaired B-Cell differentiation 19 .…”

Section: Introductionmentioning

confidence: 99%

Functional Activation of Osteoclast Commitment in Chronic Lymphocytic Leukaemia: a Possible Role for RANK/RANKL Pathway

Marini

Bruno

Fiz

et al. 2017

Sci Rep

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Skeletal erosion has been found to represent an independent prognostic indicator in patients with advanced stages of chronic lymphocytic leukaemia (CLL). Whether this phenomenon also occurs in early CLL phases and its underlying mechanisms have yet to be fully elucidated. In this study, we prospectively enrolled 36 consecutive treatment-naïve patients to analyse skeletal structure and bone marrow distribution using a computational approach to PET/CT images. This evaluation was combined with the analysis of RANK/RANKL loop activation in the leukemic clone, given recent reports on its role in CLL progression. Bone erosion was particularly evident in long bone shafts, progressively increased from Binet stage A to Binet stage C, and was correlated with both local expansion of metabolically active bone marrow documented by FDG uptake and with the number of RANKL + cells present in the circulating blood. In immune-deficient NOD/Shi-scid, γcnull (NSG) mice, administration of CLL cells caused an appreciable compact bone erosion that was prevented by Denosumab. CLL cell proliferation in vitro correlated with RANK expression and was impaired by Denosumab-mediated disruption of the RANK/RANKL loop. This study suggests an interaction between CLL cells and stromal elements able to simultaneously impair bone structure and increase proliferating potential of leukemic clone.

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“…We did not detect RANKL immunoreactivity in lymphoma cells infiltrating to the bone marrow in eight patients with systemic nodal lymphoma showing no apparent bone lesions. Interestingly, however, a case with follicular lymphoma infiltrating to the bone marrow was reported to show RANKL expression by lymphoma cells and enhancement of osteoclastic bone destruction (40). Therefore, RANKL is aberrantly expressed only in a limited number of B-cell non -Hodgkin's lymphoma clones, but once expressed it may promote osteoclastic bone destruction particularly when such lymphoma cells arise in or infiltrate to the bone marrow.…”

Section: Discussionmentioning

confidence: 99%

Malignant B-Lymphoid Cells with Bone Lesions Express Receptor Activator of Nuclear Factor-κB Ligand and Vascular Endothelial Growth Factor to Enhance Osteoclastogenesis

Shibata¹,

Abe²,

Hiura³

et al. 2005

Clinical Cancer Research

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Purpose: Receptor activator of nuclear factor-nB ligand (RANKL) is a key mediator of osteoclastogenesis. Because certain types of tumor cells aberrantly express RANKL, and because bone destruction also develops in B-cell lymphomas of bone origin, we investigated RANKL expression and the mechanisms of osteoclastogenesis in B-lymphoid neoplasms. Experimental Design and Results: Immunohistochemistry of bone specimens resected from patients with primary B-cell lymphoma of bone with bone destruction revealed that lymphoma cells express RANKL as well as vascular endothelial cell growth factor (VEGF). The tumor cells isolated from the bone specimens enhanced osteoclastogenesis in vitro. In contrast, B-cell lymphoma infiltrating to the bone marrow without bone destruction did not express RANKL. Both RANKL and VEGF were expressed by a portion of B-lymphoid cell lines, including Daudi and IM-9. These RANKL-expressing tumor cells enhanced osteoclastogenesis from RAW264.7 cells and human monocyte-derived preosteoclasts in the absence of stromal cells/osteoblasts in a RANKL-dependent manner. Furthermore, conditioned media from Daudi cells enhanced transmigration of preosteoclasts that was inhibited by anti-VEGF antibody, suggesting that tumor cell^derived VEGF mediates recruitment of osteoclast precursors. Moreover, cocultures of B-lymphoid cell lines with osteoclasts enhanced the growth of B-lymphoid cells. Conclusions: Some malignant B cells aberrantly express functional RANKL as well as VEGF to enhance osteoclastogenesis. The coexpression of RANKL and VEGF may also contribute to the close cellular interactions with osteoclastic cells, thereby forming a vicious cycle between osteoclastic bone destruction and tumor expansion in bone.Certain types of B-lymphoid neoplasms, such as lymphoma of bone origin and multiple myeloma, exclusively develop and expand in the skeleton. These tumors cause lytic bone lesions, which lead to the debilitating clinical symptoms including intractable bone pain and disabling fractures. In those destructive bone lesions, osteoclasts seem to surround tumor cells and actively resorb bone. Several bone-resorbing factors, including parathyroid hormone -related protein (1), interleukin (IL)-1h (2 -4), and IL-6 (3 -5), have been implicated as causative factors for bone destruction in multiple myeloma, and recent reports including those from ourselves indicate that a C-C chemokine, macrophage inflammatory protein-1a and macrophage inflammatory protein-1h, plays an important role in the development of lytic bone lesions by multiple myeloma (6 -10). However, the pathogenesis as well as the mechanism of bone destruction by B-cell lymphoma of bone origin is largely unknown.Binding of receptor activator of nuclear factor-nB ligand (RANKL; refs. 11 -13) to its receptor (RANK; ref. 14) is essential for the enhancement of osteoclast differentiation, activation, and survival, whereas its decoy receptor, osteoprotegerin (15), inhibits RANKL-RANK signaling. Along with RANKL, macrophage colony-stimulating f...

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RANKL expression in a case of follicular lymphoma

Cited by 8 publications

References 6 publications

A case of fatal osteolytic hypercalcemia complicated with IgG4-related ophthalmic disease leading to renal failure

A case of fatal osteolytic hypercalcemia complicated with IgG4-related ophthalmic disease leading to renal failure

Functional Activation of Osteoclast Commitment in Chronic Lymphocytic Leukaemia: a Possible Role for RANK/RANKL Pathway

Malignant B-Lymphoid Cells with Bone Lesions Express Receptor Activator of Nuclear Factor-κB Ligand and Vascular Endothelial Growth Factor to Enhance Osteoclastogenesis

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