RNAi-mediated silencing of TEL/AML1 reveals a heat-shock protein- and survivin-dependent mechanism for survival

The TEL/AML1 fusion gene results from the most frequent t(12;21)(p13;q22) translocation in childhood acute lymphoblastic leukemia (ALL). Its contribution to transformation is largely unknown, in particular with respect to survival and apoptosis. We therefore silenced TEL/AML1 expression in leukemic REH cells by RNA inhibition, which eventually led to programmed cell death. Microarray and 2D gel electrophoresis data demonstrated a differential regulation of heat-shock proteins (HSPs), among them HSP90, as well as of its client, survivin. Consistent with these findings, ectopic expression of TEL/AML1 in Ba/F3 cells increased protein levels of HSP90 and survivin and conferred resistance to apoptotic stimuli. Our data suggest that TEL/AML1 not only contributes to leukemogenesis by affecting an antiapoptotic network but also seems to be indispensable for maintaining the malignant phenotype. The functional relationship between TEL/AML1, HSP90, and survivin provides the rational for targeted therapy, be it the fusion gene or the latter 2 proteins.     

Echocardiography detection of intracavitary ventricular tumors

Intracavitary ventricular tumors were found in 3 male patients (newborn, and 18 and 23 years old) by 2-D echocardiography (metastasis of an osteogenic sarcoma in the right ventricle, teratoma embryonale growing from the retroperitoneum into the right ventricle, rhabdomyoma of the left ventricle). They all showed a uniform echo pattern and two of them were pedunculated. Wall motility, valves and cardiac dimensions were normal. In each case diagnosis was confirmed intraoperatively or at autopsy. Clinically the metastasis of the osteogenic sarcoma presented as obstruction of the superior vena cava, whereas the teratoma embryonale imitated tricuspid valve disease. The rhabdomyoma caused a systolic murmur and severe postpartal sinus bradycardia. It was successfully removed on the basis of echocardiography alone. 2-D echocardiography is a reliable, noninvasive diagnostic tool for evaluation of intracavitary, ventricular tumors.     

Demonstration and differentiation of circulating immune complexes in chronic inflammatory rheumatic diseases using a semiautomated PEG-precipitation laser nephelometer test

Circulating immune complexes were determined in rheumatoid arthritis and systemic lupus erythematosus using a semiautomated PEG-precipitation laser-nephelometer technique. Immunoglobulins IgA, IgG and IgM as well as complement proteins C3c and C4 were quantitatively determined in 2.75% PEG-precipitates. The PEG-precipitates obtained from the sera of healthy controls, SLE patients, and RA subjects displayed different protein patterns. In RA sera a significant elevation of all investigated proteins was found. In SLE sera, a significant increase of IgG, IgA, IgM, and C3 was found, whereas C4 was significantly reduced as compared to the controls. Typical values for a calculated IgG/C4 ratio in circulating immune complexes were obtained for RA and SLE. In RA this ratio remained unchanged in different activity stages and was found in seropositive as well as in seronegative sera. Thus circulating immune complexes from SLE and RA sera differ with respect to the degree of complement-dependent solubilization.