Race-specific features and outcomes of nodular lymphocyte-predominant Hodgkin lymphoma: Analysis of the National Cancer Data Base.

BACKGROUND: The incidence of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is higher among African Americans than among other races, but to the authors' knowledge, the characteristics of NLPHL in this population have not been evaluated. The authors compared clinical features, treatments, and survival of black and white patients with NLPHL using the National Cancer Data Base. METHODS: The authors extracted the records of 602 black and 1950 white patients with NLPHL who were diagnosed between 1998 and 2011. Overall survival (OS) was compared using the log-rank test. RESULTS: Black patients were on average younger than white patients (median age, 42 years vs 45 years; P =.0001), more often female (49% vs 29%; P<.0001), and more likely to have the axillary lymph nodes as the primary disease site (25% vs 17%; P =.0002). They also had unfavorable socioeconomic characteristics, a higher rate of no treatment in patients with early-stage disease, and a longer time to therapy initiation (median, 53.5 days vs 47 days; P<.0001). Despite this, the authors found no significant difference between the races with regard to stage distribution or survival (P =.39). OS at 7 years was 90.1% in patients with early-stage (American Joint Committee on Cancer stage IA/B, IIA) and 79.4% in patients with advanced stage (American Joint Committee on Cancer stage IIB, III/IV) NLPHL. Survival in the early stage of disease was not found to be significantly different after various treatment strategies (stratified log-rank P = .18), except that the administration of chemotherapy was associated with a better outcome in black patients (log-rank P =.011 vs P =.81 for white patients). CONCLUSIONS: Differences in clinical presentation suggest the interaction of race-specific and sex-specific susceptibility factors for NLPHL. Further research is needed to elucidate these factors, and to investigate possible heterogeneous effects of treatments by race. Clinical trials comparing standard treatment strategies are unlikely to detect differences in OS among patients with early-stage NLPHL.

hBub1 negatively regulates p53 mediated early cell death upon mitotic checkpoint activation.

Our previous studies showed that the depletion of the outer kinetochore protein hBub1 upon activation of spindle assembly checkpoint (SAC) primarily triggers early cell death mediated by p53 rather than aneuploidy. Here, we report that phosphorylation of p53 at Ser37 is critical for proapoptotic activity upon SAC activation. Furthermore, we show that p53 physically interacts with hBub1 at kinetochores in response to mitotic spindle damage suggesting a direct role for hBub1 in the suppression of p53 mediated cell death. This observation is further substantiated by the inhibition of p53 mediated transactivation of the proapoptotic target genes, PUMA and BAX, by hBub1 in SAC activated cells. In summary, our data from these and our previous studies strongly suggest that in response to SAC activation, hBub1 acts as a negative regulator of p53 mediated early cell death in a novel checkpoint pathway. On the translational medicine front, it is tempting to speculate that by disabling hBub1 in p53 proficient cancer cells, apoptosis may be induced as a therapeutic approach to eradicate the tumor cells.