Hematological cancers in individuals infected by HIV

Blood ◽  
2021 ◽  
Author(s):  
Antonino Carbone ◽  
Emanuela Vaccher ◽  
Annunziata Gloghini
Keyword(s):  
Kaposi Sarcoma ◽  
B Cell Lymphoma ◽  
Castleman Disease ◽  
International Agency ◽  
Term Survival ◽  
Multicentric Castleman Disease ◽  
Barr Virus ◽  
Hematological Cancers ◽  
Epstein Barr ◽  
Cytokine Dysregulation

HIV infection increases cancer risk and is linked to cancers associated to infectious agents classified as carcinogenic to humans by the International Agency for Research on Cancer. Lymphomas represent one of the most frequent malignancies among individuals infected by HIV. Diffuse large B-cell lymphoma remains a leading cancer after the introduction of combined antiretroviral therapy (cART). The incidence of other lymphomas including Burkitt lymphoma, primary effusion lymphomas, and plasmablastic lymphoma of the oral cavity remain stable, while the incidence of Hodgkin lymphoma and Kaposi sarcoma-associated herpesvirus (KSHV)-associated Multicentric Castleman Disease has increased. The heterogeneity of lymphomas in individuals infected by HIV likely depends on the complexity of involved pathogenetic mechanisms, i.e. HIV-induced immunosuppression, genetic abnormalities, cytokine dysregulation, co-infection with the gamma-herpesviruses, Epstein Barr virus and KSHV, and the dysregulation of the immune responses controlling these viruses. In the modern cART era, standard treatments for HIV-associated lymphoma including stem cell transplantation in relapsed/refractory disease, mirrors that of the general population. The combination of cART and anti neoplastic treatments has resulted in remarkable prolongation of long-term survival. However, oncolytic and immunotherapic strategies, and therapies targeting specific viral oncogenes will need to be developed primarily.

scholarly journals Tumor suppressor genes FHIT and WWOX are deleted in primary effusion lymphoma (PEL) cell lines

Blood ◽  
2011 ◽  
Vol 118 (7) ◽  
pp. e32-e39 ◽  
Author(s):  
Debasmita Roy ◽  
Sang-Hoon Sin ◽  
Blossom Damania ◽  
Dirk P. Dittmer
Keyword(s):  
Fragile Site ◽  
Primary Effusion Lymphoma ◽  
Snp Array ◽  
Kaposi Sarcoma ◽  
B Cell Lymphoma ◽  
Host Chromosome ◽  
Barr Virus ◽  
Genomic Aberrations ◽  
Host Genetic ◽  
Epstein Barr

Abstract Primary effusion lymphoma (PEL) is a diffuse-large B-cell lymphoma with poor prognosis. One hundred percent of PELs carry the genome of Kaposi sarcoma–associated herpesvirus and a majority are coinfected with Epstein-Barr virus (EBV). We profiled genomic aberrations in PEL cells using the Affymetrix 6.0 SNP array. This identified for the first time individual genes that are altered in PEL cells. Eleven of 13 samples (85%) were deleted for the fragile site tumor suppressors WWOX and FHIT. Alterations were also observed in the DERL1, ETV1, RASA4, TPK1, TRIM56, and VPS41 genes, which are yet to be characterized for their roles in cancer. Coinfection with EBV was associated with significantly fewer gross genomic aberrations, and PEL could be segregated into EBV-positive and EBV-negative clusters on the basis of host chromosome alterations. This suggests a model in which both host genetic aberrations and the 2 viruses contribute to the PEL phenotype.

EBV+ HHV-8+ Multicentric Castleman Disease With Plasmablastic Aggregates in an HIV+ Man: An Evolving Clinicopathologic Entity

2017 ◽  
Vol 26 (4) ◽  
pp. 338-341 ◽  
Author(s):  
Aditya Shivane ◽  
Amy Pearce ◽  
Nadia Khatib ◽  
Mark E. F. Smith
Keyword(s):  
Human Herpesvirus ◽  
Cervical Lymphadenopathy ◽  
Castleman Disease ◽  
Hiv Positive ◽  
Herpesvirus 8 ◽  
Multicentric Castleman Disease ◽  
Barr Virus ◽  
Positive Individual ◽  
Epstein Barr

We report a case of EBV+ and HHV-8+ multicentric Castleman disease with plasmablastic aggregates in an HIV-positive individual. A 41-year-old man presented in early 2015 with fevers, sweats, weight loss, intractable itching, and on subsequent testing was found to be HIV positive. Investigations showed cervical lymphadenopathy and splenomegaly. He was treated for HIV and his symptoms resolved. His symptoms recurred in January 2016, and a provisional diagnosis of multicentric Castleman disease was entertained. The HHV-8 (human herpesvirus-8) and EBV (Epstein-Barr virus) viral load was elevated. A left supraclavicular lymph node core biopsy was performed, which showed features of multicentric Castleman disease with plasmablastic aggregates that are EBV (EBER) and HHV-8 positive. He responded well to rituximab treatment and remains well with no symptoms at recent follow-up.

scholarly journals Epstein–Barr virus enhances genome maintenance of Kaposi sarcoma-associated herpesvirus

2018 ◽  
Vol 115 (48) ◽  
pp. E11379-E11387 ◽  
Author(s):  
Rachele Bigi ◽  
Justin T. Landis ◽  
Hyowon An ◽  
Carolina Caro-Vegas ◽  
Nancy Raab-Traub ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Primary Effusion Lymphoma ◽  
Kaposi Sarcoma ◽  
B Cell Lymphoma ◽  
Nuclear Antigen ◽  
Genome Maintenance ◽  
Barr Virus ◽  
Single Positive ◽  
Infected Cells ◽  
Epstein Barr

Primary effusion lymphoma (PEL) is a B cell lymphoma that is always associated with Kaposi’s sarcoma-associated herpesvirus (KSHV) and in many cases also with Epstein–Barr virus (EBV); however, the requirement for EBV coinfection is not clear. Here, we demonstrate that adding exogenous EBV to KSHV+single-positive PEL leads to increased KSHV genome maintenance and KSHV latency-associated nuclear antigen (LANA) expression. To show that EBV was necessary for naturally coinfected PEL, we nucleofected KSHV+/EBV+PEL cell lines with an EBV-specific CRISPR/Cas9 plasmid to delete EBV and observed a dramatic decrease in cell viability, KSHV genome copy number, and LANA expression. This phenotype was reversed by expressing Epstein–Barr nuclear antigen 1 (EBNA-1)in trans, even though EBNA-1 and LANA do not colocalize in infected cells. This work reveals that EBV EBNA-1 plays an essential role in the pathogenesis of PEL by increasing KSHV viral load and LANA expression.

scholarly journals Lymphotropic Viruses EBV, KSHV and HTLV in Latin America: Epidemiology and Associated Malignancies. A Literature-Based Study by the RIAL-CYTED

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2166
Author(s):  
Paola Chabay ◽  
Daniela Lens ◽  
Rocio Hassan ◽  
Socorro María Rodríguez Pinilla ◽  
Fabiola Valvert Gamboa ◽  
...  
Keyword(s):  
Latin America ◽  
Nk Cell ◽  
Cell Lymphoma ◽  
Kaposi Sarcoma ◽  
B Cell Lymphoma ◽  
Close Correlation ◽  
Developed Countries ◽  
Barr Virus ◽  
The North ◽  
Epstein Barr

The Epstein–Barr virus (EBV), Kaposi sarcoma herpesvirus (KSHV) and human T-lymphotropic virus (HTLV-1) are lymphomagenic viruses with region-specific induced morbidity. The RIAL-CYTED aims to increase the knowledge of lymphoma in Latin America (LA), and, as such, we systematically analyzed the literature to better understand our risk for virus-induced lymphoma. We observed that high endemicity regions for certain lymphomas, e.g., Mexico and Peru, have a high incidence of EBV-positive lymphomas of T/NK cell origin. Peru also carries the highest frequency of EBV-positive classical Hodgkin lymphoma (HL) and EBV-positive diffuse large B cell lymphoma, not otherwise specified (NOS), than any other LA country. Adult T cell lymphoma is endemic to the North of Brazil and Chile. While only few cases of KSHV-positive lymphomas were found, in spite of the close correlation of Kaposi sarcoma and the prevalence of pathogenic types of KSHV. Both EBV-associated HL and Burkitt lymphoma mainly affect young children, unlike in developed countries, in which adolescents and young adults are the most affected, correlating with an early EBV seroconversion for LA population despite of lack of infectious mononucleosis symptoms. High endemicity of KSHV and HTLV infection was observed among Amerindian populations, with differences between Amazonian and Andean populations.

Epstein-Barr Virus-associated Diffuse Large B-cell Lymphoma Arising on Cardiac Prostheses

2010 ◽  
Vol 34 (3) ◽  
pp. 377-384 ◽  
Author(s):  
Dylan V. Miller ◽  
Dennis J. Firchau ◽  
Rebecca F. McClure ◽  
Paul J. Kurtin ◽  
Andrew L. Feldman
Keyword(s):  
B Cell ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Barr Virus ◽  
Large B Cell Lymphoma ◽  
Epstein Barr ◽  
Large B Cell

Coexistence of disseminated Kaposi sarcoma and multicentric Castleman disease in an HIV-infected patient under viral suppression

2021 ◽  
Vol 32 (3) ◽  
pp. 286-289
Author(s):  
I-Fan Lin ◽  
Jiun-Nong Lin ◽  
Tsung-Heng Tsai ◽  
Chao-Tien Hsu ◽  
Yu-Ying Wu ◽  
...  
Keyword(s):  
Viral Load ◽  
Viral Suppression ◽  
Liposomal Doxorubicin ◽  
Kaposi Sarcoma ◽  
Castleman Disease ◽  
Severe Thrombocytopenia ◽  
Multicentric Castleman Disease ◽  
Progressive Pancytopenia ◽  
One Year ◽  
Cd4 T Cell Count

Coexistence of multicentric Castleman disease and Kaposi sarcoma is rare and might be missed without an experienced pathologists’ interpretation. A 46-year-old man had been diagnosed with HIV infection and treated with combination antiretroviral therapy of dolutegravir/abacavir/lamivudine (Triumeq) for one year. The latest viral load was 49 copies/mL and CD4 T-cell count was 192 cells/uL. He was admitted due to fever off and on, splenomegaly, general lymphadenopathy, and severe thrombocytopenia for two months. Biopsy of a purplish skin lesion and gastric tissue showed Kaposi sarcoma. The pathology of inguinal lymph nodes revealed coexistence of Kaposi sarcoma and multicentric Castleman disease. The plasma Kaposi sarcoma herpesvirus viral load was 365,000 copies/mL. During hospitalization, progressive pancytopenia and spiking fever persisted, and he died of multi-organ failure before completion of chemotherapeutic treatments with rituximab plus liposomal doxorubicin.

scholarly journals KSHV- and EBV-associated germinotropic lymphoproliferative disorder

Blood ◽  
2002 ◽  
Vol 100 (9) ◽  
pp. 3415-3418 ◽  
Author(s):  
Ming-Qing Du ◽  
Tim C. Diss ◽  
Hongxiang Liu ◽  
Hongtao Ye ◽  
Rifat A. Hamoudi ◽  
...  
Keyword(s):  
Lymphoproliferative Disorder ◽  
Gene Rearrangement ◽  
Primary Effusion Lymphoma ◽  
Kaposi Sarcoma ◽  
Castleman Disease ◽  
Lymphoproliferative Disorders ◽  
Multicentric Castleman Disease ◽  
Tissue Sections ◽  
Response To Chemotherapy ◽  
Ig Heavy Chain

Abstract Kaposi sarcoma–associated herpesvirus (KSHV) is known to be associated with 3 distinct lymphoproliferative disorders: primary effusion lymphoma (PEL), multicentric Castleman disease (MCD), and MCD-associated plasmablastic lymphoma. We report 3 cases of a previously undescribed KSHV-associated lymphoproliferative disorder. The disease presented as localized lymphadenopathy and showed a favorable response to chemotherapy or radiotherapy. Histologically, the lymphoproliferation is characterized by plasmablasts that preferentially involved germinal centers of the lymphoid follicles, forming confluent aggregates. They were negative for CD20, CD27, CD79a, CD138, BCL6, and CD10 but showed monotypic κ or λ light chain. Clusters of CD10+CD20+ residual follicle center cells were identified in some of the follicles. The plasmablasts were positive for both KSHV and EBV, and most of them also expressed viral interleukin-6 (vIL-6). Unexpectedly, molecular analysis of whole tissue sections or microdissected KSHV-positive aggregates demonstrated a polyclonal or oligoclonal pattern of immunoglobulin (Ig) gene rearrangement. The plasmablasts showed somatic mutation and intraclonal variation in the rearranged Ig genes, and one case expressed switched Ig heavy chain (IgA), suggesting that they originated from germinal center B cells. We propose calling this distinctive entity “KSHV-associated germinotropic lymphoproliferative disorder.”

scholarly journals Latent KSHV infection increases the vascular permeability of human endothelial cells

Blood ◽  
2011 ◽  
Vol 118 (19) ◽  
pp. 5344-5354 ◽  
Author(s):  
Christophe Guilluy ◽  
Zhigang Zhang ◽  
Prasanna M. Bhende ◽  
Lisa Sharek ◽  
Ling Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Permeability ◽  
Latent Infection ◽  
Primary Effusion Lymphoma ◽  
Kaposi Sarcoma ◽  
Castleman Disease ◽  
Cell Junctions ◽  
Paracrine Factors ◽  
Kshv Infection ◽  
Multicentric Castleman Disease

Abstract Kaposi sarcoma–associated herpesvirus (KSHV) is associated with 3 different human malignancies: Kaposi sarcoma (KS), primary effusion lymphoma, and multicentric Castleman disease. The KS lesion is driven by KSHV-infected endothelial cells and is highly dependent on autocrine and paracrine factors for survival and growth. We report that latent KSHV infection increases the vascular permeability of endothelial cells. Endothelial cells with latent KSHV infection display increased Rac1 activation and activation of its downstream modulator, p21-activated kinase 1 (PAK1). The KSHV-infected cells also exhibit increases in tyrosine phosphorylation of vascular endothelial (VE)–cadherin and β-catenin, whereas total levels of these proteins remained unchanged, suggesting that latent infection disrupted endothelial cell junctions. Consistent with these findings, we found that KSHV-infected endothelial cells displayed increased permeability compared with uninfected endothelial cells. Knockdown of Rac1 and inhibition of reactive oxygen species (ROS) resulted in decreased permeability in the KSHV-infected endothelial cells. We further demonstrate that the KSHV K1 protein can activate Rac1. Rac1 was also highly activated in KSHV-infected endothelial cells and KS tumors. In conclusion, KSHV latent infection increases Rac1 and PAK1 activity in endothelial cells, resulting in the phosphorylation of VE-cadherin and β-catenin and leading to the disassembly of cell junctions and to increased vascular permeability of the infected endothelial cells.

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