Apoptosis and cell proliferation capacity in AKR lymphoma malignancy variants.

Dysregulation in apoptotic cell death has recently emerged as a factor in tumorigenesis, but its effect in tumor progression is not yet established. In the present study we evaluated the levels of proliferative and apoptotic cell fractions in a T-cell lymphoma tumor progression model. We compared these features and the expression of apoptosis-related genes in primary tumors of several AKR lymphoma malignancy variants. According to DNA flow cytometry, a considerable proportion of cells (35-40%) was in the proliferative (S + G2/M) phase in all variants, but a slight augmentation with increasing malignancy was noted. Apoptotic cell content was, unexpectedly, the lowest in the less malignant variant. This might be due to the higher content in macrophages observed in this variant, which possibly partly eliminated apoptotic bodies. We found an increase in bcl-2 level with increasing malignancy that was probably counterbalanced by the simultaneous increase observed in the Fas receptor.

Release from apoptosis correlates with tumor progression in the AKR lymphoma.

Disturbance of apoptosis is an established factor in tumorigenesis. The role of apoptosis in tumor progression is not yet clear. In the present study we compared the tendency to spontaneous apoptosis (and the proliferative capacity) of tumor cells derived from primary (PT) and metastatic tumor (MT) cells of several AKR lymphoma variants. Apoptosis-related gene expression was also compared. Our results indicate that release from apoptosis has a role in the tumor progression of this T cell lymphoma. At the cellular level, a markedly lower apoptotic tendency was observed in MT than in PT cells. The existence of macrophages only in PT also supports the presence of apoptotic cells in local but not in MTs. By contrast, proliferative capacity does not determine tumor aggressiveness in this system. At the molecular level, we found a higher staining intensity for bcl-2 in MT than in PT cells, suggesting that bcl-2 might be responsible for the reduced apoptosis in MT compared to PT cells. Evidence for p53 overexpression was found in the MT cells of one of the variants but in none of the PT. Comparison of Fas receptor, unexpectedly showed an increased expression in MT versus PT cells, possibly indicating resistance to Fas-induced apoptosis in the MT cells.

Geographic variance in the frequency of the t(14;18) translocation in follicular lymphoma: an Israeli series compared to the world.

It has been suggested that differences in the frequency of the t(14;18) translocation in follicular lymphoma might explain ethno-geographic variation in the incidence of these tumors. We tested Israeli follicular lymphoma patients for the frequency of the t(14;18) translocation, and reviewed the published literature, comparing the frequency in our series with data from different parts of the world. Tissue specimens from 36 Israeli follicular lymphoma patients were tested for presence of the translocation by PCR amplification of the MBR breakpoint. Twenty-two of the 36 patients (61%) tested positive. A systematic search of the literature yielded 35 papers reporting the frequency of the t(14;18) translocation in follicular lymphoma. We analyzed cytogenetic data and molecular data separately. For each method, data were pooled from all studies within each of three geographical regions - USA, East Asia and Europe. Pooled data from cytogenetic studies show a low frequency of the translocation in the Far East (38%) compared to the USA (71%), with an intermediate frequency found in Europe (61%). Molecular studies show a similar frequency of the translocation in the Far East and Europe, significantly lower than the frequency in pooled data from American studies. The frequency in our Israeli series is relatively high, comparable to that detected in the USA. We suggest that the apparent geographical differences we describe are unlikely to be caused by a difference in the biology of the tumor, and are more likely due to technical and methodological factors. We conclude that it is unlikely that differences in the frequency of the t(14;18) translocation explain the difference in the epidemiology of lymphoma between East and West.

Familial persistent pulmonary hypertension.

We report three siblings who presented with a clinical picture of persistent pulmonary hypertension of newborn and died between 4 and 15 days of age. Pulmonary artery pressure in all was above systemic values, with a right to left shunt via either the foramen ovale or ductus arteriosus, or both. Histology of the pulmonary vascular bed showed extension of muscle into small arteries which are normally non-muscular.