HHV8-Negative Primary Effusion Lymphoma of B-Cell Lineage: Two Cases and a Comprehensive Review of the Literature.

2013

Saini N, Hochberg EP, Linden EA, Jha S, Grohs HK, Sohani AR.

Source

Department of Internal Medicine, North Shore Medical Center, Salem, MA 01970, USA.

Abstract

Primary effusion lymphoma (PEL) is a rare extranodal lymphoma that typically presents in a body cavity in the absence of a detectable tumor mass and that occurs predominantly in immunosuppressed individuals. The neoplastic lymphoid cells are frequently infected with human herpes virus 8 (HHV8), also known as Kaposi sarcoma herpes virus (KSHV). We describe two HIV-negative patients who presented with primary effusion lymphoma of B-cell lineage involving the pleural cavity, but whose tumor cells lacked infection by HHV8. We review the English language literature of HHV8-negative PEL of B-cell lineage and compare these lymphomas to HHV8-associated PEL with regard to clinical and pathological characteristics, therapy, and outcome.

Full Text Article

Case Reports in Oncological Medicine

MCL1 is deregulated in subgroups of diffuse large B-cell lymphoma.

Dec 21, 2012

Wenzel SS, Grau M, Mavis C, Hailfinger S, Wolf A, Madle H, Deeb G, Dörken B, Thome M, Lenz P, Dirnhofer S,Hernandez-Ilizaliturri FJ, Tzankov A, Lenz G.

Source

Department of Hematology, Oncology and Tumor Immunology, Molecular Cancer Research Center, Charité - Universitätsmedizin Berlin, Germany.

Abstract

Keywords: 

MCL1, diffuse large B-cell lymphoma, aCGH, apoptosis, therapy resistance

MCL1 is an anti-apoptotic member of the BCL2 family that is deregulated in various solid and hematological malignancies. However, its role in the molecular pathogenesis of diffuse large B-cell lymphoma (DLBCL) is unclear. We analyzed gene expression profiling data from 350 DLBCL patient samples and detected that activated B-cell-like (ABC) DLBCLs express MCL1 at significantly higher levels compared to germinal center B-cell-like (GCB) DLBCL patient samples (p=2.7 x 10(-10)). Immunohistochemistry confirmed high MCL1 protein expression predominantly in ABC DLBCL in an independent patient cohort (n=249; p=0.001). To elucidate molecular mechanisms leading to aberrant MCL1 expression, we analyzed array comparative genomic hybridization (aCGH) data of 203 DLBCL samples and identified recurrent chromosomal gains/amplifications of the MCL1 locus that occurred in 26% of ABC DLBCLs. In addition, aberrant STAT3 signaling contributed to high MCL1 expression in this subtype. Knockdown of MCL1 as well as treatment with the BH3-mimetic obatoclax induced apoptotic cell death in MCL1 positive DLBCL cell lines. In summary, MCL1 is deregulated in a significant fraction of ABC DLBCLs and contributes to therapy resistance. These data suggest that specific inhibition of MCL1 might be utilized therapeutically in a subset of DLBCLs.Leukemia accepted article preview online, 21 December 2012; doi:10.1038/leu.2012.367.

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