Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Cancer Cell. 2010 Oct 19;18(4):353-66. doi: 10.1016/j.ccr.2010.09.009.
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.
T 淋巴细胞白血病（T-ALL）向 T 淋巴母细胞淋巴瘤（T-LBL）进展的分子事件仍难以捉摸。在我们的斑马鱼模型中，Myc 与 bcl-2 的同时过表达加速了 T-LBL 的发病，同时抑制了向 T-ALL 的进展。T-LBL 细胞未能侵入血管，并显示出同种细胞间黏附性增加和自噬的证据。对临床活检标本的进一步分析显示，与 T-ALL 相比，人类 T-LBL 中自噬和 BCL2、S1P1 和 ICAM1 的水平增加。T-LBL 细胞中 S1P1 信号的抑制导致体外同种细胞黏附减少，体内肿瘤细胞浸润增加。因此，T-LBL 中的血管内浸润和血液传播阻断是由于 S1P1 信号的上调、ICAM1 的表达增加和同种细胞间黏附性的增强。
