Activation of tumor suppressor genes is frequently associated with cytogenetic loss in specific chromosomal loci. The chromosomal segment 6q15-23 is deleted in 4-20% of acute lymphoblastic leukemias and in non-Hodgkin's lymphomas, and may harbor a relevant tumor suppressor gene(s) involved in development of these lymphoid malignancies. Because this segment has also been reported to undergo deletions in a wide variety of nonhematological tumors including breast cancer, prostatic cancer, malignant melanoma, and pancreatic cancer, inactivation of the putative tumor suppressor(s) may also be committed to genesis of multiple tumor types.
In this study, we analyzed 388 samples of hematopoietic tumors for deletions within a long arm of chromosome 6 by fluorescent in situ hybridization (FISH) method in order to define a minimum overlapping deletion. Forty nine different PAC/BAC clones were derived from known STS markers in 6q and used as probes for FISH analysis. Deletions were distributed over the region defined by D6S284 and WI4227, spanning from 6q15 to 6q23. Although the frequency of deletions was highest in the locus defined by D6S1563 and D6S1543, regions of isolated, non-overlapping deletions were also identified. These results indicate that multiple tumor suppressor loci may exist in the long arm of chromosome 6, and give a basis for future attempts to isolate tumor suppressor genes in this relevant region.

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Dendritic cells are specialized antigen-presenting cells with a unique ability to prime effective immune responses. This may give them a special importance in disease states known to have an immunological basis and to induce immune responses to viral and other tumor antigens not only in mouse but also in human. The potency of DCs as inducers of T cell-mediated immunity can be analyzed at 3 levels: 1) antigen uptake and processing, leading to presentation of MHC-peptide complexes; 2) membrane molecules, like CD40, 54, 58, 80 and 86, and cytokines, like IL-12, leading to strong stimulation of T cell growth and differentiation; 3) in vivo localization, leading to movement from the periphery to the T cell areas of lymphoid organs to initiate immunity. These physiological abilities of DCs are closely related to a set of events termed maturation. Functional differences between several types of DCs may merely reflect differences in the maturation or activation status of the same cells. On the other hand, considerable phenotypic and functional heterogeniety has been documented within the DC system. There is now strong evidence that separate hematopoietic lineages of DCs exist. An understanding of the different pathways of DC development provides new insights into the diversity of DC functions in vivo, such as immunity versus tolerance.

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The white pulp (WP) and marginal zone (MZ) constitute the immunologically active compartment of the human spleen. In the WP, there are two distinct regions, the periarteriolar lymphoid sheath (PALS) and the lymph follicle (LF). The basic framework of the PALS, LF and MZ consists of reticulum cells and reticulin fibers. A distinct microenvironment, is formed in the reticular framework of the PALS, LF and MZ, respectively. Immunophenotype of the reticulum cells is heterogeneous in the PALS, LF and MZ. Composition of extracellular matrix proteins of the reticulin fibers is also different in the PALS, LF and MZ. The reticular framework of the PALS, LF and MZ is specialized into heterogeneous components and plays a role in the formation of the distinct microenvironment specific for lymphoid subclasses and the lymphocyte homing and segregation mechanism. In the ontogeny of the PALS, LF and MZ, the development of the heterogeneity of the reticular framework is related with the organization of the PALS, LF and MZ.

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