(Elsevier BV, 2010) Feng, Hui; Stachura, David L.; White, Richard; Gutierrez, Alejandro; Zhang, Lu; Sanda, Takaomi; Jette, Cicely A.; Testa, Joseph R.; Neuberg, Donna; Langenau, David; Kutok, Jeffery Lorne; Zon, Leonard; Traver, David; Fleming, Mark; Kanki, John P.; Look, A.
The 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.
