Endothelial progenitor cells display clonal restriction in multiple myeloma

BACKGROUND: In multiple myeloma (MM), increased neoangiogenesis contributes to tumor growth and disease progression. Increased levels of endothelial progenitor cells (EPCs) contribute to neoangiogenesis in MM, and, importantly, covary with disease activity and response to treatment. In order to understand the mechanisms responsible for increased EPC levels and neoangiogenic function in MM, we investigated whether these cells were clonal by determining X-chromosome inactivation (XCI) patterns in female patients by a human androgen receptor assay (HUMARA). In addition, EPCs and bone marrow cells were studied for the presence of clonotypic immunoglobulin heavy-chain (IGH) gene rearrangement, which indicates clonality in B cells; thus, its presence in EPCs would indicate a close genetic link between tumor cells in MM and endothelial cells that provide tumor neovascularization. METHODS: A total of twenty-three consecutive patients who had not received chemotherapy were studied. Screening in 18 patients found that 11 displayed allelic AR in peripheral blood mononuclear cells, and these patients were further studied for XCI patterns in EPCs and hair root cells by HUMARA. In 2 patients whose EPCs were clonal by HUMARA, and in an additional 5 new patients, EPCs were studied for IGH gene rearrangement using PCR with family-specific primers for IGH variable genes (V(H)). RESULTS: In 11 patients, analysis of EPCs by HUMARA revealed significant skewing (≥ 77% expression of a single allele) in 64% (n = 7). In 4 of these patients, XCI skewing was extreme (≥ 90% expression of a single allele). In contrast, XCI in hair root cells was random. Furthermore, PCR amplification with V(H )primers resulted in amplification of the same product in EPCs and bone marrow cells in 71% (n = 5) of 7 patients, while no IGH rearrangement was found in EPCs from healthy controls. In addition, in patients with XCI skewing in EPCs, advanced age was associated with poorer clinical status, unlike patients whose EPCs had random XCI. CONCLUSION: Our results suggest that EPCs in at least a substantial subpopulation of MM patients are related to the neoplastic clone and that this is an important mechanism for upregulation of tumor neovascularization in MM

Lossy JPEG Compression in Quantitative Angiography: the Role of X-ray Quantum Noise

In medical imaging, contrary to applications in the consumer market, the use of irreversible or lossy compression is still in its beginnings. This is due to the suspected risk of compromising the diagnostic content. Many studies have been performed, but it was not until 2008 that national activities in different countries resulted in recommendations for the safe use of irreversible image compression in clinical practice. Quantitative coronary angiography (QCA), however, poses a special problem, since here a large variation in published maximum compression factors has strengthened the general concerns about the use of lossy techniques. Up to now, the reason for the variation has not been thoroughly investigated. Reasons for the discrepancies in published compression factors are determined in this study. Since JPEG compression reduces the quantum noise of the X-ray images, the impact of compression is overestimated when interpreting any change in local diameter as an error. By taking into consideration the quantitative effect of quantum noise in QCA, it is shown that the influence of JPEG compression can be neglected for compression factors up to ten at clinically applicable X-ray doses. This limit is comparable to that found by visual analysis for aesthetic image quality. Future studies on image compression effects should take the interaction with quantum noise explicitly into consideration