Feng, HuiStachura, David L.White, RichardGutierrez, AlejandroZhang, LuSanda, TakaomiJette, Cicely A.Testa, Joseph R.Neuberg, DonnaLangenau, DavidKutok, Jeffery LorneZon, LeonardTraver, DavidFleming, MarkKanki, John P.Look, A.2014-10-142010Feng, Hui, David L. Stachura, Richard M. White, Alejandro Gutierrez, Lu Zhang, Takaomi Sanda, Cicely A. Jette, et al. 2010. T-Lymphoblastic Lymphoma Cells Express High Levels of BCL2, S1P1, and ICAM1, Leading to a Blockade of Tumor Cell Intravasation. Cancer Cell 18, no. 4: 353–366.1535-61081878-3686http://nrs.harvard.edu/urn-3:HUL.InstRepos:13041314The molecular events underlying the progression of T-lymphoblastic lymphoma (T-LBL) to acute T-lymphoblastic leukemia (T-ALL) remain elusive. In our zebrafish model, concomitant overexpression of bcl-2 with Myc accelerated T-LBL onset while inhibiting progression to T-ALL. The T-LBL cells failed to invade the vasculature and showed evidence of increased homotypic cell-cell adhesion and autophagy. Further analysis using clinical biopsy specimens revealed autophagy and increased levels of BCL2, S1P1, and ICAM1 in human T-LBL compared with T-ALL. Inhibition of S1P1 signaling in T-LBL cells led to decreased homotypic adhesion in vitro and increased tumor cell intravasation in vivo. Thus, blockade of intravasation and hematologic dissemination in T-LBL is due to elevated S1P1 signaling, increased expression of ICAM1, and augmented homotypic cell-cell adhesion.en-USJournal Article2014-10-1410.1016/j.ccr.2010.09.009