To investigate the relationship between Bcl-2 protein expression and cell proliferation at single-cell level in B-cell lymphomas using double-labelling techniques.
Mantle cell lymphoma (MCL) is a rare, aggressive subtype of non-Hodgkin lymphoma with a poor prognosis and high recurrence rate. It seldom affects the Waldeyer's ring let alone the nasopharynx. Patients usually present at late stages of the disease leading to poor failure-free and overall survival rates. Intensive chemotherapy regimes and autologous stem cell transplantation have reported increased survival rates. We report a relapsed case of nasopharyngeal MCL, which previously occurred in the gastrointestinal tract. The patient had undergone a hemicolectomy for colon intussusception secondary to the intraluminal lymphoma mass. He was unable to complete the treatment regime for MCL due to the adverse side effects. Oropharyngeal mass was discovered during routine outpatient follow-up, which was confirmed as nasopharyngeal MCL. We discuss the prognosis, disease progression, and possible treatments.
Aim: Abnormal expression patterns of beta-tubulin isotypes may provide a molecular rationale for the behaviour of lymphoma subtypes. In the present study class II and III beta-tubulin expression was assessed in non-neoplastic and neoplastic lymphoid tissues with reference to potential utility as new tumour biomarkers. Methods and results: In this cross-sectional study class II and III beta-tubulin expression was assessed in 304 neoplastic and 20 normal lymphoid tissues using qualitative and semi-quantitative immunohistochemistry. Class II beta-tubulin was found to be positive in the germinal centres, mantle zone and interfollicular regions of normal lymphoid tissues. It was also expressed in 15/15 (100%) lymphoblastic lymphomas, 229/231 (99%) mature B cell lymphomas, 22/22 (100%) T/NK-cell lymphomas and 36/36(100%) classical Hodgkin lymphomas. Class III beta-tubulin in contrast was germinal centre restricted and more selective, being found mainly in classical Hodgkin lymphomas (34/36 (94%)). It was also expressed in 58/171(34%) DLBCL, 11/12 (92%) mantle cell lymphomas and 6/6 (100%) Burkitt lymphomas. Other mature B cell, T/NK cell lymphomas and precursor lymphoblastic lymphomas were usually negative. Conclusions: Class II beta-tubulin shows ubiquitous expression in neoplastic and non-neoplastic lymphoisd tissues. In contrast, Class III beta-tubulin is germinal centre-restricted. Its consistent expression in classical Hodgkin lymphomas may point to use in the identification of Reed-Sternberg and Hodgkin cells. Its expression in a proportion of DLBCL, Burkitt and mantle cell lymphomas is of interest as this may be related to their aggressiveness.
Bortezomib is the first proteasomal inhibitor (PI) to be used therapeutically for treating relapse cases of multiple myeloma and mantle cell lymphoma. A proposed mechanism for its action is that it prevents the proteasomal degradation of proapoptotic proteins, leading to enhanced apoptosis. Although the α subunit of hypoxia-inducible factor (HIF)-1 is not degraded with bortezomib treatment, the heterodimeric HIF-1 fails to transactivate target genes. HIF-1 and HIF-2 are related hypoxia-inducible transcription factors that are important for the survival of hypoxic tumor cells. The majority of reports have focused on the effects of bortezomib on the transcriptional activities of HIF-1, but not HIF-2. The present study investigated the effects of bortezomib on HIF-2 activity in cancer cells with different levels of HIF-1α and HIF-2α subunits. HIF-α subunit levels were detected using specific antibodies, while HIF transcriptional activities were evaluated using immunodetection, reverse transcription-polymerase chain reaction and luciferase reporter assay. Bortezomib treatment was found to suppress the transcription and expression of CA9, a HIF-1-specific target gene; however, it had minimal effects on EPO and GLUT-1, which are target genes of both HIF-1 and HIF-2. These data suggest that bortezomib attenuates the transcriptional activity only of HIF-1, and not HIF-2. This novel finding on the lack of an inhibitory effect of bortezomib on HIF-2 transcriptional activity has implications for the improvement of design and treatment modalities of bortezomib and other PI drugs.