Rearrangement and overexpression of the BCL-1/PRAD-1 gene in intermediate lymphocytic lymphomas and in t(11q13)-bearing leukemias

The t(11;14)(q13;q32) translocation and its molecular counterpart, BCL- 1 rearrangement, are consistent features of intermediate lymphocytic lymphoma (ILL). Rearrangement is thought to deregulate the nearby PRAD- 1/BCL-1 proto-oncogene that is a newly identified member of the cyclin family. To characterize further the association between rearrangement of chromosome 11q13 and over-expression of BCL-1. Southern blot analysis was performed in 33 cases of ILL, 5 cases of t(11;14)- associated leukemias, and 1 case of leukemia carrying a variant translocation t(11;19)(q13;q13) using three separate BCL-1 locus probes. When RNA was available, BCL-1 expression was assessed by Northern blot analysis. DNA from 19 of 33 ILL (57%) showed BCL-1 rearrangement, 16 involving the major translocation cluster (MTC) region and 3 involving a new breakpoint cluster located in the 5' flanking region of the BCL-1 gene. DNA from 3 of 6 t(11q13)-associated leukemias demonstrated a rearrangement involving the MTC. Northern blot analysis showed that BCL-1 was overexpressed in 14 of 15 ILL and in all leukemias analyzed (included the t(11;19) leukemia) relative to normal and malignant lymphoid tissues. These results constitute additional elements in favor of the role of BCL-1 in lymphoid neoplasia and allow us to speculate about its mechanisms of activation.     

Lympho-epidermal interactions in patients receiving human Langerhans cell free cultured epidermal allografts as a skin substitute

Human Langerhans cell free epithelia can be cultured in vitro, and then can be used as epidermal allografts (EAG) without evidence of rejection. We studied the cellular basis of this phenomenon with mixed epidermal cell lymphocyte reactions (MELR). The capacity of donor-derived epidermal cells to stimulate allogeneic control or recipient cells was abolished when stimulatory cells were Langerhans cell-free cultured keratinocytes and respondors were obtained prior to grafting. Donor-type cultured keratinocytes were able to induce a low response by host-derived cells in assays conducted 2, 4 and 6 weeks after grafting, but not thereafter. They were unable to stimulate allogeneic cells unrelated to the recipient. The ability of crude epidermal suspensions with 2–4% Langerhans cells to stimulate host-derived cells did not increase with time after grafting. No secondary type MELR could be evidenced, suggesting that grafting of EAG did not induce an in vivo immunization to class I antigens expressed by cultured epidermal cells. Lastly, host-derived Langerhans cells were not able to restore the allostimulatory ability of Langerhans cell free epidermal cells from EAG donors when tested against host-derived cells. This suggests that host-derived Langerhans cells which colonize the grafts during the first few weeks following grafting cannot act in the presentation of foreign keratinocyte-bound antigens, which may account for the absence of rejection noted.