Molecular analysis of immunoglobulin variable genes in human immunodeficiency virus-related non-Hodgkin's lymphoma reveals implications for disease pathogenesis and histogenesis

Capello, Daniela; Martini, Maurizio; Gloghini, Annunziata; Cerri, Michaela; Rasi, Silvia; Deambrogi, Clara; Rossi, Davide; Spina, Michele; Tirelli, Umberto; Larocca, Luigi Maria; Carbone, Antonino; Gaïdano, Gianluca

doi:10.3324/haematol.12705

Cited by 26 publications

(29 citation statements)

References 56 publications

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“…In addition, approximately two-thirds of HIV-DLBCLs have BCL6 mutations, and about 50% of cases have aberrant somatic hypermutations in other proto-oncogenes, such as PIM1, PAX5, RhoH/TTF, and MYC, all of which may contribute to the development of these neoplasms. 106,107,121,122 In addition, comparison of EBV þ and EBV À HIV-related DLBCLs shows that the EBV þ cases have fewer gene copy number changes, indicating that this virus may play a pathogenetic role in EBV þ cases. 123,124 Diffuse large B-cell lymphomas in immunocompetent patients, as determined by gene expression profiling and by immunophenotypic expression patterns, can be divided into clinically relevant groups: germinal center and activated B cell/type 3 (nongerminal center) which are composed of approximately equal numbers of cases in each category.…”

Section: 116mentioning

confidence: 99%

Lymphoid Proliferations Associated With Human Immunodeficiency Virus Infection

Chadburn

Abdul-Nabi

Teruya

et al. 2013

Archives of Pathology &Amp; Laboratory Medicine

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Context.—Individuals who are immune deficient are at an increased risk for developing lymphoproliferative lesions and lymphomas. Human immunodeficiency virus (HIV) infection is 1 of 4 clinical settings associated with immunodeficiency recognized by the World Health Organization (WHO) in which there is an increased incidence of lymphoma and other lymphoproliferative disorders. Objectives.—To describe the major categories of benign lymphoid proliferations, including progressive HIV-related lymphadenopathy, benign lymphoepithelial cystic lesions, and multicentric Castleman disease, as well as the different types of HIV-related lymphomas as defined by the WHO. The characteristic morphologic, immunophenotypic, and genetic features of the different entities will be discussed in addition to some of the pathogenetic mechanisms. Data Sources.—The WHO classification of tumors of hematopoietic and lymphoid tissues (2001 and 2008), published literature from PubMed (National Library of Medicine), published textbooks, and primary material from the authors' current and previous institutions. Conclusions.—HIV infection represents one of the clinical settings recognized by the WHO in which immunodeficiency-related lymphoproliferative disorders may arise. Although most lymphomas that arise in patients with HIV infection are diffuse, aggressive B-cell lesions, other lesions, which are “benign” lymphoid proliferations, may also be associated with significant clinical consequences. These lymphoproliferations, like many other immunodeficiency-associated lymphoproliferative disorders, are often difficult to classify. Studies of HIV-associated lymphoid proliferations will continue to increase our understanding of both the immune system and lymphomagenesis.

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Section: 116mentioning

confidence: 99%

Lymphoid Proliferations Associated With Human Immunodeficiency Virus Infection

Chadburn

Abdul-Nabi

Teruya

et al. 2013

Archives of Pathology &Amp; Laboratory Medicine

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“…This stimulation could lead to rearrangements in the immunoglobulin variable genes (IGV) that ultimately lead to the development and expansion of the lymphoma clone. In this issue of Haematologica Capello et al 5 have shown that over 90% of HIV-related lymphomas (especially DLBCL and BL) had aberrant somatic hypermutation of IGHV genes, and a skewed IGHV repertoire was observed in specific clinicopathologic categories, supporting the hypothesis that both subtypes of HIV-related lymphomas originate from B cells that have terminated germinal center transformation. In contrast, some cases of primary CNS lymphoma were devoid of somatic hypermutation of the IGHV genes, suggesting that they may represent transformation of B cells experiencing preterminal germinal center-independent differentiation.…”

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confidence: 80%

“…Many of these advances will come from basic and translational research. Research on the mechanisms utilized by lymphomas in immunodeficient individuals (that presented in the article by Capello et al 5 in this issue of the journal is a good example) may have applications in lymphomas in other situations of immunosuppression and even in those arising in immunocompetent patients.…”

Section: © F E R R a T A S T O R T I F O U N D A T I O N © F E R R A mentioning

confidence: 99%

“…Some of the well-described complications in this population include subsequent malignancies, cataracts, pulmonary complications, endocrine dysfunction, osteonecrosis, chronic kidney disease, and impairment in functional status due to persistent, chronic graft-versus-host disease (GVHD). [5][6][7] Details regarding cardiovascular dysfunction after HCT are now emerging. [8][9][10] In this issue of the journal, Tichelli et al publish the results of their retrospective study designed to describe the magnitude of risk of and associated risk factors for the development of arterial events after allogeneic HCT.…”

Section: Supported In Part By Grants Rd06/0020/1056 From Ret-ics and mentioning

confidence: 99%

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Human immunodeficiency virus-related non-Hodgkin's lymphoma

Ribera¹,

Navarro²

2008

Haematologica

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F e r r a t a S t o r t i F o u n d a t i o n © F e r r a t a S t o r t i F o u n d a t i o nEditorialsaccount. The results of the combination of full dose chemotherapeutic regimens and HAART have improved the response rate and the survival of patients with HIV-related lymphomas ( Figure 1). In two comparative studies, the prognosis of patients with HIVrelated lymphomas was similar to that observed in non-immunosuppressed patients with non-Hodgkin's lymphoma of the same histological type. 11,12 The main prognostic factors for these patients were the IPI score and the CD4 lymphocyte count at the time of diagnosis. 13 In addition, it is of note that chemotherapy and concomitant HAART do not cause prolonged suppression of lymphocyte subsets 14 and, most importantly, that the immmunological response to HAART has a positive effect on the survival of these patients. 15 Treatment of patients with HIV-related BL has evolved from reduced-dose or CHOP-like chemotherapy regimens with resultant poor clinical outcomes to more Burkitt-oriented short, intensive multiagent chemotherapy including fractionated cyclophosphamide, high-dose methotrexate and cytarabine. The widespread use of HAART has overcome much of the reluctance to pursue intensive regimens in AIDS-related BL. Specific therapies for these patients have includ- Although these regimens have been associated with significant toxicity in HIV-related BL, they have resulted in an improvement in the response rate and in the survival probability of up to 50%. In the ALL3/97 study, no significant differences were observed in the survival of patients with HIV-related or unrelated BL. 18Again, patients with an immunological response to HAART had a better prognosis than those who did not take or did not respond to HAART.Mimicking non-Hodgkin's lymphoma in nonimmunosuppressed patients, the next step was to use immunochemotherapy for both AIDS-related DLBCL and BL. Three phase II trials with chemotherapy (CHOP in two trials 19,20 and CDE in one 21) and rituximab have shown that immunochemotherapy with concomitant administration of HAART is feasible, safe and effective, with complete responses in more than 70% of patients and survival probabilities ranging from 65% to 75%. However, from the data of these phase II trials it is difficult to determine the contribution of rituximab to the overall efficacy. The only comparative trial published to date, the AMC-10 trial, 22 which compared the CHOP regimen with or without rituximab, showed a not statistically significant trend for a better response rate (57.6% vs. 47%) in the rituximab-CHOP (R-CHOP) arm, which did not translate into better survival, at least in part because of the excess number of infectious deaths in that arm (14% vs. 2%). Nevertheless, even in moderately immunosuppressed patients (i.e., those with a CD4 lymphocyte count over 100/µL) no significant benefits in terms of survival were observed in the R-CHOP arm. The inclusion of a high number of severely immunosuppressed patients in that trial could explain the inferio...

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“…8 In addition, examination of the IgH genes shows, in contrast to sporadic BL, but similar to endemic BLs, that AIDS-related BL have a relatively large number of somatic mutations, and at least some cases show evidence of antigen selection. 69,94 However, there has been no evidence of on-going mutations. 69 These findings suggest that HIV-related BL are derived from cells that have terminated the germinal center reaction, and thus are late germinal center (or memory) B cells.…”

Section: Burkitt Lymphoma (Bl)mentioning

confidence: 99%