AIDS‐related plasmablastic lymphoma with dramatic, early response to bortezomib

Bose, Prithviraj; Thompson, Christopher; Gandhi, D. G.; Ghabach, Bassam; Ozer, Howard

doi:10.1111/j.1600-0609.2009.01235.x

Cited by 45 publications

(28 citation statements)

References 8 publications

(9 reference statements)

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“…This finding is consistent with the report from Lu and colleagues (38) showing that bortezomib is effective in MDR-1 expressing leukemia cell line, K562/A02. It also supports the report by Bose and colleagues (39) where bortezomib showed marked shrinkage of the disease in a patient with HIV-positive plasmablastic lymphoma. Therefore, we believe that the use of bortezomib with or without conventional chemotherapeutic agents may be an effective treatment strategy for plasmablastic lymphomas.…”

Section: Discussionsupporting

confidence: 91%

Identification of Loss of p16 Expression and Upregulation of MDR-1 as Genetic Events Resulting from Two Novel Chromosomal Translocations Found in a Plasmablastic Lymphoma of the Uterus

Matsuki

Miyakawa

Asakawa

et al. 2011

Clinical Cancer Research

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Purpose: To establish cell lines from the patient with plasmablastic lymphoma, who was immunologically competent including negative human immunodeficiency virus (HIV) serology, and analyze the unique chromosomal translocations seen in the cell lines in order to unveil the pathogenesis of this tumor, which had no evidence of Epstein-Barr virus involvement.Experimental Design: Establishment of the cell lines was attempted by inoculating the patient's lymph node biopsy specimen subcutaneously to immunodeficient mice. Comparative genomic hybridization (CGH) array and FISH analysis were performed to identify breakpoints of the two chromosomal translocations. Of the 4 candidate genes identified by FISH analysis to be involved in the translocations, reverse transcription-PCR, Western blot, flow cytometry, and proliferation assay were performed to identify the exact genes involved.Results: Analysis of the cell lines identified loss of p16 at the protein level by chromosomal translocation of t(9;13) and upregulation of MDR-1 by t(4;7). The cell lines expressing MDR-1 acquired resistance to chemotherapeutic agents such as cisplatin and doxorubicin, but not bortezomib. Expression of B lymphoid lineage marker genes of these cell lines was negative for paired box 5 (Pax5) or PR domain containing 1, with ZNF domain (PRDM1), but was positive for X-box binding protein 1 (Xbp1).Conclusions: We established three novel cell lines of plasmablastic lymphoma. Characterization of the unique chromosomal translocation identified loss of p16 and upregulation of MDR-1 at protein level. Expression of Xbp1(s), which is involved in the maturation of plasma cells, corresponded to the plasmablastic appearance of the tumor. These cell lines may be a useful tool to understand the pathophysiology of the disease and to develop novel treatment strategies.

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Section: Discussionsupporting

confidence: 91%

Identification of Loss of p16 Expression and Upregulation of MDR-1 as Genetic Events Resulting from Two Novel Chromosomal Translocations Found in a Plasmablastic Lymphoma of the Uterus

Matsuki

Miyakawa

Asakawa

et al. 2011

Clinical Cancer Research

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“…This might explain the recently reported dramatic response of a patient with PBL of the stomach to bortezomib treatment 4 . This study underlines the importance of routine evaluation of MYC rearrangements in PBL cases as this may have prognostic and treatment choice implications 10 .…”

Section: Discussionmentioning

confidence: 90%

“…However, the pathogenesis of this disease has not been fully elucidated and the normal cell counterpart from which PBL takes origin is still to be determined. It is difficult to distinguish PBL from extramedullary plasmacytomas (EMPC) or multiple myeloma (MM) with plasmablastic morphology and the possibility that PBL may be related to these neoplasms has previously been proposed 1,3,4 .…”

Section: Introductionmentioning

confidence: 99%

Dominant genetic aberrations and coexistent EBV infection in HIV-related oral plasmablastic lymphomas

et al. 2011

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SUMMARYWe present common cytogenetic features in the largest cohort of plasmablastic lymphoma (PBL) of the oral cavity published to date. This cohort included 45 patients, 32 of whom had a known HIV status, of which thirty one were HIV positive. Ninety eight per cent of all PBL cases were known to be EBV positive. In line with previous studies, we found that rearrangements of the MYC gene was the most common genetic abnormality seen in 60% of cases with the immunoglobulin heavy chain (IGH) locus as a partner in 51% of cases. Additional complex genetic aberrations were frequent, in particular, an increased copy number of the CCND1 gene was seen in 41% of cases with true amplification of CCND1 in 15% of cases. Aneuploidy was also observed for the BCL6 gene in 28% of cases. Interestingly, rearrangements of both IGH genes were detected in 16% of cases with t(14;18) and t(11;14) respectively involved in conjunction with a t(8;14) in two cases. These bi-allelic IGH rearrangements have not been described before in oral PBL. Our results reinforce the notion that EBV infection and MYC rearrangements are important events in the pathogenesis of oral PBL. The genetic diversity and complexity observed in these cases, underlines the importance to genetically characterise PBL patients at presentation as this may inform the choice of more effective treatment modalities.3

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“…Recent studies have reported the potential value of the proteasome inhibitor bortezomib in patients with DLBCL of NGC/ABC origin [24]; bortezomib elicits its antilymphoma effect by blocking nuclear factor B and by sensitizing NGC/ABC DLBCL patients to chemotherapy. Only one patient in our series was treated with single-agent bortezomib, achieving a short-lived PR but finally succumbing to infections [21]. There is an ongoing phase I/II trial, sponsored by the AIDS Malignancies Consortium, using bortezomib in combination with ifosfamide, carboplatin, and etoposide with or without rituximab in patients with relapsed or refractory HIV-associated non-Hodgkin's lymphoma (ClinicalTrials.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Factors in Chemotherapy-Treated Patients with HIV-Associated Plasmablastic Lymphoma

et al. 2010

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Background. Plasmablastic lymphoma (PBL) is a variant of diffuse large B-cell lymphoma commonly seen in the oral cavity of HIV-infected individuals. PBL has a poor prognosis, but prognostic factors in patients who have received chemotherapy have not been adequately evaluated.Methods. An extensive literature search rendered 248 cases of PBL, from which 157 were HIV ؉ . Seventy cases with HIV-associated PBL that received chemotherapy were identified. Whenever possible, authors of the original reports were contacted to complete clinicopathological data. Univariate analyses were performed calculating Kaplan-Meier estimates and compared using the log-rank test.Results. The mean age was 39 years, with a male predominance. The mean CD4؉ count was 165 cells/mm 3 . Advanced clinical stage was seen in 51% and extraoral

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AIDS‐related plasmablastic lymphoma with dramatic, early response to bortezomib

Cited by 45 publications

References 8 publications

Identification of Loss of p16 Expression and Upregulation of MDR-1 as Genetic Events Resulting from Two Novel Chromosomal Translocations Found in a Plasmablastic Lymphoma of the Uterus

Identification of Loss of p16 Expression and Upregulation of MDR-1 as Genetic Events Resulting from Two Novel Chromosomal Translocations Found in a Plasmablastic Lymphoma of the Uterus

Dominant genetic aberrations and coexistent EBV infection in HIV-related oral plasmablastic lymphomas

Prognostic Factors in Chemotherapy-Treated Patients with HIV-Associated Plasmablastic Lymphoma

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