to lethally irradiated Tcra2/2;Relb2/2 and Tcra2/2;Relb+/+ littermate recipient mice. We found that Tcra2/2;Relb2/2 recipient mice reconstituted with TEL-JAK2;Tcra2/2 bone marrow cells developed T-cell leukemia with delayed onset, as compared to the reconstituted Tcra2/2;Relb+/+ littermates . Two TELJAK2;Tcra2/2RTcra2/2;Relb2/2 mice even survived without leukemia for more than 60 weeks after transplantation. PCR detection of the TEL-JAK2 transgene and the wild-type Relb allele in thymocytes from these mice showed effective donor bone marrow engraftment. The two groups of mice developed severe dyspnea due to leukemic cell accumulation in the thymus and to pleural effusion containing leukemic cells. Like the original TEL-JAK2 transgenic mice, diseased chimeric mice showed leukemic cell accumulation in the bone marrow, spleen, lungs, and liver. Leukemic cells from both groups of mice expressed variable levels of CD4, CD8, RelB Promotes Leukemogenesis CD24, and CD25 cell surface markers, characteristic of bona fide TEL-JAK2 T-cell leukemia. However, in addition to a delayed onset, TEL-JAK2;Tcra2/2RTcra2/2;Relb2/2 diseased mice presented significantly reduced accumulation of leukemic cells in the thymus and lymph nodes, as compared to TEL-JAK2; Tcra2/2RTcra2/2;Relb+/+ mice, indicating 
that the disease evolved more slowly in lymphoid organs from Relb-deficient chimeras. A similar difference in tumor burden was observed in an independent experiment comparing leukemia development between Tcra2/2;Relb2/2 and Tcra2/2;Relb+/2 recipients. Taken together, these results show that RelB has a 17804601 specific, non-redundant function in radiation-resistant thymic and lymph node stromal cells that facilitates TEL-JAK2-induced T-cell leukemogenesis. Discussion active T cells. Indeed, in contrast to the reported RelB-deficient phenotype, no significant inflammatory infiltrates were observed in the organs of Tcra2/2;Relb2/2 mice. Our previous results showed that TEL-JAK2 transforms immature DN and DP thymocytes. Since DN and DP thymocyte development remained unaffected in the Tcra2/2; Relb2/2 thymic microenvironment, we exclude the possibility that the delay in TEL-JAK2-induced leukemogenesis in RelB-deficient mice was simply due to a reduction in cellular targets available for oncogenic transformation. Our results thus suggest that the RelBdependent microenvironment contributes specifically to DN/DP thymocyte transformation by TEL-JAK2. Mouse RelB deficiency results in impaired lymphoid organ microarchitecture, affecting to varying degrees the development of thymus, spleen, lymph nodes, and Peyer’s patches. Stromal defects in these lymphoid organs likely account for the observed delay in TEL-JAK2-induced leukemogenesis in Tcra2/2; Relb2/2 mice. Since RelB-deficient diseased mice presented reduced thymic and lymph node tumor load compared to RelB-proficient controls, we conclude that defects in these organs were responsible for the delay in leukemogenesis. Although lymph node development is strongly affected by the lack of RelB, the direct cellular defects associated with RelB deficiency in this organ are as yet unknown. In contrast, it has been shown that RelB-deficient 18690793 thymi lack a Ganetespib defined medulla and mTECs and show a strong reduction in CD80+DEC205+ dendritic cell numbers secondary to the defect in thymic architecture and mTECs. Accordingly, Tcra2/2;Relb2/2 mice showed no discernable thymic medulla and no UEA-1+ mTECs. TCRa-deficient mice also show thymic archit
