New Insights into Diffuse Large B-Cell Lymphoma Pathobiology

Solimando, Antonio Giovanni; Annese, Tiziana; Tamma, Roberto; Ingravallo, Giuseppe; Maiorano, Eugenio; Vacca, Angelo; Specchia, Giorgina; Ribatti, Doménico

doi:10.3390/cancers12071869

Cited by 46 publications

(33 citation statements)

References 168 publications

(216 reference statements)

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“…In DLBCL, TGF-β pathway is inactivated at the level of SMAD1 43,44 such that downstream enhancement of this pathway would likely benefit survival outcomes. Genes in the unfavorable signatures tended to activate the acute immune system response and angiogenesis, both of which are associated with metastatic disease and poor prognosis through a constitutively activated STAT3 pathway 45 . Genes in the favorable signatures tended to promote organ development and hematopoiesis, which may be associated with cell differentiation, and activate Wnt signaling while downregulating adaptive immune response systems.…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling-based risk prediction and profiles of immune infiltration in diffuse large B-cell lymphoma

et al. 2021

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The clinical risk stratification of diffuse large B-cell lymphoma (DLBCL) relies on the International Prognostic Index (IPI) for the identification of high-risk disease. Recent studies suggest that the immune microenvironment plays a role in treatment response prediction and survival in DLBCL. This study developed a risk prediction model and evaluated the model’s biological implications in association with the estimated profiles of immune infiltration. Gene-expression profiling of 718 patients with DLBCL was done, for which RNA sequencing data and clinical covariates were obtained from Reddy et al. (2017). Using unsupervised and supervised machine learning methods to identify survival-associated gene signatures, a multivariable model of survival was constructed. Tumor-infiltrating immune cell compositions were enumerated using CIBERSORT deconvolution analysis. A four gene-signature-based score was developed that separated patients into high- and low-risk groups. The combination of the gene-expression-based score with the IPI improved the discrimination on the validation and complete sets. The gene signatures were successfully validated with the deconvolution output. Correlating the deconvolution findings with the gene signatures and risk score, CD8+ T-cells and naïve CD4+ T-cells were associated with favorable prognosis. By analyzing the gene-expression data with a systematic approach, a risk prediction model that outperforms the existing risk assessment methods was developed and validated.

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Section: Discussionmentioning

confidence: 99%

Gene expression profiling-based risk prediction and profiles of immune infiltration in diffuse large B-cell lymphoma

et al. 2021

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“…It is generally accepted that chronic inflammatory diseases (such as SS, Hashimoto thyroiditis, Borrelia Burgdorferi dermatitis, Helicobacter pylori-associated chronic gastritis and HCV, HHV8, EBV and HTLV-1 infections) may play a role in lymphoma development, resulting in the transition from polyclonal B cell activation into monoclonal expansion of B-lymphocytes. The transition into B-cell NHL only affects a minority of the aforementioned patients harboring chronic inflammatory diseases and has been associated with increased overall disease mortality rate [ 5 , 6 , 7 , 8 , 9 , 11 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

Primary Breast Extranodal Marginal Zone Lymphoma in Primary Sjögren Syndrome: Case Presentation and Relevant Literature

Ingravallo

Maiorano

Moschetta

et al. 2020

JCM

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The association between autoimmune diseases, mostly rheumatoid arthritis, systemic lupus erythematosus, celiac disease and Sjögren syndrome, and lymphoma, has been widely demonstrated by several epidemiologic studies. By a mechanism which has not yet been entirely elucidated, chronic activation/stimulation of the immune system, along with the administration of specific treatments, may lead to the onset of different types of lymphoma in such patients. Specifically, patients affected by Sjögren syndrome may develop lymphomas many years after the original diagnosis. Several epidemiologic, hematologic, and histological features may anticipate the progression from Sjögren syndrome into lymphoma but, to the best of our knowledge, a definite pathogenetic mechanism for such progression is still missing. In fact, while the association between Sjögren syndrome and non-Hodgkin lymphoma, mostly extranodal marginal zone lymphomas and, less often, diffuse large B-cell, is well established, many other variables, such as time of onset, gender predilection, sites of occurrence, subtype of lymphoma, and predictive factors, still remain unclear. We report on a rare case of primary breast lymphoma occurring three years after the diagnosis of Sjögren syndrome in a 57-year-old patient. The diagnostic work-up, including radiograms, core needle biopsy, and histological examination, is discussed, along with emerging data from the recent literature, thus highlighting the usefulness of breast surveillance in Sjögren syndrome patients.

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“…The transition to B-cell NHL only affects a minority of the aforementioned chronic patients, but it has been associated with a surplus in the overall disease mortality rate. [5][6][7][8][9][10]13] As for chronic inflammation, Bizjak et al in 2015 [26] extensively reviewed the role of inflammation related to breast silicone implants and not-breast silicone prostheses (such as cardiac pacemakers and defibrillators, cardiac valvular and testicular/penile prostheses) in lymphoma development. They assumed that the pathogenic mechanism of chronic inflammation in predisposed individuals, though not well understood but possibly related to the severe scarring of peri-implant tissues with persistent inflammation, could lead to chronic activation of the local/systemic immune system, with polyclonal and possibly monoclonal lymphocytic activation.…”

Section: Discussionmentioning

confidence: 99%

“…Patients with autoimmune diseases represent 5% of NHL patients, but lymphoma surely is the most severe complication occurring during SS patients' follow-up. [5][6][7][8][9][10][11] As widely discussed by Vasaitis et al in a recent population-based study, [27] data available in the literature on lymphoma subtypes in SS patients, such as as gender differences in lymphoma risk and prevalence in comparison with the general population, are not uniform at all. [27] Also, median time from SS diagnosis until the development of breast lymphoma is related to the observational period, which rarely exceeds 10 years in almost all studies, thus distorting the overall epidemiological data.…”

Section: Discussionmentioning

confidence: 99%

“…[27][28][29][30][31] Nevertheless, although the association between SS (and other autoimmune diseases) and NHL is nowadays well defined, its true biological mechanism has not been fully elucidated yet. [1][2][3][4][5][6][7]10,11,13,27] In an update on prognostic markers of lymphoma development in SS patients, Retamozo et al (2019) [32] stated that such patients show a 7-fold increased risk of lymphoma than systemic lupus erythematosus patients, 4-fold than rheumatoid arthritis patients, and globally >10 folds than the general population. [5,32] The same Authors listed, point-to-point evaluated and discussed the different prognostic/predictive factors emerging from previously published studies: epidemiologic markers (age and sex); clinical markers (parotid enlargement, dry mouth and eyes, arthralgias, splenomegaly, lymphadenopathy, skin purpura/vasculitis); laboratory markers (systemic activity, hypergamma/raised IgG, CD4/CD8 ≤ 0.8, raised beta2-microglobulin, raised B-cell activating factors, anemia, leukopenia, lymphopenia, neutropenia, ANA, rheumatoid factor, Anti-Ro/La, low C4, C3 and CH 50 levels, cryoglobulins, mIgs); histological markers (focus score and ectopic primary or secondary follicle).…”

Section: Discussionmentioning

confidence: 99%

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Primary Breast Extranodal Marginal Zone Lymphoma in Primary Sjögren Syndrome: Case Presentation and Relevant Literature

Ingravallo

Maiorano

Moschetta

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

The association between autoimmune diseases, mostly rheumatoid arthritis, systemic lupus erythematous, celiac disease and Sjögren syndrome, and lymphoma has been widely demonstrated by several epidemiologic studies. By a not yet entirely elucidated mechanism, chronic activation/stimulation of the immune system, along with the administration of specific treatments, may lead to persistent stimulation of both of B- and T-cells, and to the onset of different types of lymphoma in such patients. Specifically, patients affected by may develop lymphomas may years after the original diagnosis. Several epidemiologic, hematologic and histological factors may anticipate the progression from Sjögren syndrome into lymphoma but, to the best of our knowledge, a definite pathogenetic mechanism for such progression is still missing. In fact, while the association between Sjögren syndrome and non-Hodgkin lymphoma, mostly diffuse large B-cell and extranodal marginal zone lymphomas is well established, many other variables, such as time of onset, gender predilection, sites of occurrence, subtype of lymphoma and predictive factors still remain unclear. We report on a rare case of primary breast lymphoma occurring three years after the diagnosis of Sjögren syndrome in a 57 y.o. patient. The diagnostic work-up, including radiograms, core needle biopsy and histological examination are discussed, along with emerging data from the recent literature, thus highlighting the usefulness of breast surveillance in Sjögren syndrome patients.

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New Insights into Diffuse Large B-Cell Lymphoma Pathobiology

Cited by 46 publications

References 168 publications

Gene expression profiling-based risk prediction and profiles of immune infiltration in diffuse large B-cell lymphoma

Gene expression profiling-based risk prediction and profiles of immune infiltration in diffuse large B-cell lymphoma

Primary Breast Extranodal Marginal Zone Lymphoma in Primary Sjögren Syndrome: Case Presentation and Relevant Literature

Primary Breast Extranodal Marginal Zone Lymphoma in Primary Sjögren Syndrome: Case Presentation and Relevant Literature

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