The transcription factor NF-B regulates expression of genes that are involved in inflammation, immune response, viral infection, cell survival, and division. However, the role of NF-B in hypertrophic growth of terminally differentiated cardiomyocytes is unknown. Here we report that NF-B activation is required for hypertrophic growth of cardiomyocytes. In cultured rat primary neonatal ventricular cardiomyocytes, the nuclear translocation of NF-B and its transcriptional activity were stimulated by several hypertrophic agonists, including phenylephrine, endothelin-1, and angiotensin II. The activation of NF-B was inhibited by expression of a ''supersuppressor'' I B␣ mutant that is resistant to stimulationinduced degradation and a dominant negative I B kinase (IKK␤) mutant that can no longer be activated by phosphorylation. Furthermore, treatment with phenylephrine induced I B␣ degradation in an IKK-dependent manner, suggesting that NF-B is a downstream target of the hypertrophic agonists. Importantly, expression of the supersuppressor I B␣ mutant or the dominant negative IKK␤ mutant blocked the hypertrophic agonist-induced expression of the embryonic gene atrial natriuretic factor and enlargement of cardiomyocytes. Conversely, overexpression of NF-B itself induced atrial natriuretic factor expression and cardiomyocyte enlargement. These findings suggest that NF-B plays a critical role in the hypertrophic growth of cardiomyocytes and may serve as a potential target for the intervention of heart disease.

Key Points Based on their impact on treatment and survival, ACAs in CML were stratified into good and poor prognostic groups. ACAs in the good prognostic group showed no adverse impact on survival when they emerged from chronic phase or at the initial CML diagnosis.

BackgroundPlasmablastic lymphoma (PBL) is a rare aggressive neoplasm with lymphoid and plasmacytic differentiation that is commonly associated with immunodeficiency and an unfavorable prognosis. Clinicopathologic features have been largely derived from cases reports and small series with limited outcome analyses.Patients and methodsThe demographic, clinicopathologic features, and clinical outcomes of a cohort of 61 patients with PBL were reviewed and analyzed.ResultsPatients had a median age of 49 years (range 21–83 years) and most (49/61; 80 %) were men. Human immunodeficiency virus (HIV) status was available for 50 patients: 20 were HIV-positive and 30 HIV-negative. Twenty-three patients were immunocompetent. Abdominal/gastrointestinal complaints were the most common presenting symptoms, reported in 14 of 47 (30 %) of patients. At presentation, 24 of 43 (56 %) patients had stage III or IV disease. Epstein-Barr virus (EBV) was detected in 40 of 57 (70 %) cases. MYC rearrangement was identified in 10/15 (67 %) cases assessed, and MYC overexpression was seen in all cases assessed regardless of MYC rearrangement status. HIV-positive patients were significantly younger than those who were HIV-negative (median 42 vs. 58 years; p = 0.006). HIV-positive patients were also significantly more likely to have EBV-positive disease compared with HIV-negative patients (19/19, 100 % vs. 15/29, 52 %; p = 0.002). Patients who received CHOP chemotherapy tended to have better overall survival (OS) compared with those who received hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) (p = 0.078). HIV status had no impact on OS. Patients with EBV-positive PBL had a better event-free survival (EFS) (p = 0.047) but not OS (p = 0.306). Notably, OS was adversely impacted by age ≥50 years (p = 0.013), stage III or IV disease (p = <0.001), and lymph node involvement (p = 0.008).ConclusionsThe most significant prognostic parameters in patients with PBL are age, stage, and, to a lesser extent, EBV status. In this study, two-thirds of PBL cases assessed were associated with MYC rearrangement and all showed MYC overexpression.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-015-0163-z) contains supplementary material, which is available to authorized users.