Polycomb-group proteins in hematopoietic stem cell regulation and hematopoietic neoplasms.

The equilibrium between self-renewal and differentiation of hematopoietic stem cells is regulated by epigenetic mechanisms. In particular, Polycomb-group (PcG) proteins have been shown to be involved in this process by repressing genes involved in cell-cycle regulation and differentiation. PcGs are histone modifiers that reside in two multi-protein complexes: Polycomb Repressive Complex 1 and 2 (PRC1 and PRC2). The existence of multiple orthologs for each Polycomb gene allows the formation of a multitude of distinct PRC1 and PRC2 sub-complexes. Changes in the expression of individual PcG genes are likely to cause perturbations in the composition of the PRC, which affect PRC enzymatic activity and target selectivity. An interesting recent development is that aberrant expression of, and mutations in, PcG genes have been shown to occur in hematopoietic neoplasms, where they display both tumor-suppressor and oncogenic activities. We therefore comprehensively reviewed the latest research on the role of PcG genes in normal and malignant blood cell development. We conclude that future research to elucidate the compositional changes of the PRCs and methods to intervene in PRC assembly will be of great therapeutic relevance to combat hematological malignancies.

Unaltered strong immunohistochemical expression of CD44-v6 and -v5 isoforms during development and progression of oral squamous cell carcinomas.

The present study was designed to immunolocalize CD44-v6 and -v5 isoforms in normal, dysplastic and malignant oral mucosa as well as in primary and metastatic oral squamous cell carcinomas. Routinely formalin-fixed and paraffin-embedded tissues of 100 oral carcinoma patients were immunohistochemically investigated following wet autoclave antigen retrieval. Both CD44-v6 and -v5 epitopes were uniformly strongly expressed on the cell surface of basal and intermedial epithelial cells of normal and dysplastic mucosa and in all primary and metastatic squamous cell carcinomas with the exception of end-differentiated keratinizing cells. Our results strongly suggest that CD44-v6 and -v5 isoform expression is not altered during development and progression of oral carcinomas. Thus, they seem to be irrelevant factors in the prediction of prognosis in this type of cancer.