In this issue

Enumeration of Circulating Tumor Cells

The presence of circulating tumor cells (CTC) in patients with metastatic carcinomas is associated with poor progression and overall survival. Due to their low occurrence in blood, accurate enumeration and characterization of CTC is critically important. Traditional identification of CTC is done by expert reviewers. Scholtens and coworkers introduce a new method that automates the identification of CTC, by CellTracks TDI, using the Random Forest method. Events are classified into five categories: intact CTC, apoptotic CTC, CTC debris, leukocytes, and debris. Classification of events by the automated classifier is not only comparable to that of five expert reviewers but also 100% reproducible. Automated classification of events by CellTracks TDI eliminates reviewer error thereby improving the stratification of patients into favorable and unfavorable groups.

In this issue, page 138

FRET as a diagnostic tool?

Characteristic GM₁ lipid raft relocalizations of immunologically important receptors – MHCI, ICAM-1, IL-2R, IL-15R, CD44 and CD59 – induced by Crohn's disease on the molecular (∼nm) level have been reported by Damjanovich and coworkers on CD4+ T-cells isolated from patients' lymph nodes by using pairwise flow cytometric FRET measurements. An interesting feature of their data is that not only the expression levels of receptors have been changed (reduction for MHCI, increases for IL-2/15R, CD44, and GM₁ lipids) but also the donor-acceptor distances (increasing between MHCI molecules, decreasing between IL-2/15R, CD44, CD59 and MHCI), suggesting real geometric rearrangements (conformation and/or proximity changes) of receptors, and ultimately possible changes in signaling properties by these receptors in disease. However, the decision on whether the experienced geometric changes are really followed by altered signaling properties awaits further studies on the level of the relevant intracellular signaling cascades (Src kinases, JAKs, STATs). Intriguing questions regarding the connection between transmembrane signaling and morphology of receptor clusters and using the latter as a diagnostic tool have also been raised.

In this issue: page 149

Human and rhesus erythrocytes: cross-reactivity for antibody binding

The rhesus macaque animal model is regularly utilized for studies of erythroid biology. However, analyses of rhesus erythrocytes have been hampered by the lack of erythroid specific antibodies that may be useful for flow cytometry, as well as comparative studies with human erythrocytes. By studying a group of commercially available antibodies that bind human erythrocytes, Byrnes and coworkers identified a widely available monoclonal antibody that binds specifically to rhesus and human erythrocytes. The anti-CD233 (band 3) antibody was generated and previously reported by the International Blood Reference Laboratory in Bristol, England. Comparative genomics analyses suggest that the antibody may bind to an external loop of the membrane protein that is conserved in both species. This work may be helpful for advancing studies that utilize the rhesus model to explore malaria, gene therapy and hematopoiesis research.

In this issue: page 165