S1P-S1PR3-RAS promotes the progression of S1PR3hi TAL1+ T-cell acute lymphoblastic leukemia that can be effectively inhibited by an S1PR3 antagonist

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	S1P-S1PR3-RAS promotes the progression of S1PR3hi TAL1+ T-cell acute lymphoblastic leukemia that can be effectively inhibited by an S1PR3 antagonist
	Zhu, D; Jiang, TT; Ma, DY; Zhang, HY; Zhang, J; Lv, WQ; Gong, MY; Wang, HB; Liu, ZY; Su, HY; Zeng, LM; Liu, S; Tang, S; Yang, BJ; Tshavuka, FI; Fu, G; Liu, ZD; Peng, DY; Liu, HY; Yan, ZJ; Cao, ZY; Zhao, H; He, TC; Yu, J; Shu, Y; Zou, L
	2023
发表期刊	LEUKEMIA
ISSN	0887-6924
卷号	37 期号:10 页码:1982-1993
摘要	TAL1(+) T-cell acute lymphoblastic leukemia (T-ALL) is a distinct subtype of leukemia with poor outcomes. Through the cooperation of co-activators, including RUNX1, GATA3, and MYB, the TAL1 oncoprotein extends the immature thymocytes with autonomy and plays an important role in the development of T-ALL. However, this process is not yet well understood. Here, by investigating the transcriptome and prognosis of T-ALL from multiple cohorts, we found that S1PR3 was highly expressed in a subset of TAL1(+) T-ALL (S1PR3(hi) TAL1(+) T-ALL), which showed poor outcomes. Through pharmacological and genetic methods, we identified a specific survival-supporting role of S1P-S1PR3 in TAL1(+) T-ALL cells. In T-ALL cells, TAL1-RUNX1 up-regulated the expression of S1PR3 by binding to the enhancer region of S1PR3 gene. With hyperactivated S1P-S1PR3, T-ALL cells grew rapidly, partly by activating the KRAS signal. Finally, we assessed S1PR3 inhibitor TY-52156 in T-ALL patient-derived xenografts (PDXs) mouse model. We found that TY-52156 attenuated leukemia progression efficiently and extended the lifespan of S1PR3(hi) TAL1(+) T-ALL xenografts. Our findings demonstrate that S1PR3 plays an important oncogenic role in S1PR3(hi) TAL1(+) T-ALL and may serve as a promising therapeutic target.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14120
专题	其他
推荐引用方式 GB/T 7714	Zhu, D,Jiang, TT,Ma, DY,et al. S1P-S1PR3-RAS promotes the progression of S1PR3hi TAL1+ T-cell acute lymphoblastic leukemia that can be effectively inhibited by an S1PR3 antagonist[J]. LEUKEMIA,2023,37(10):1982-1993.
APA	Zhu, D.,Jiang, TT.,Ma, DY.,Zhang, HY.,Zhang, J.,...&Zou, L.(2023).S1P-S1PR3-RAS promotes the progression of S1PR3hi TAL1+ T-cell acute lymphoblastic leukemia that can be effectively inhibited by an S1PR3 antagonist.LEUKEMIA,37(10),1982-1993.
MLA	Zhu, D,et al."S1P-S1PR3-RAS promotes the progression of S1PR3hi TAL1+ T-cell acute lymphoblastic leukemia that can be effectively inhibited by an S1PR3 antagonist".LEUKEMIA 37.10(2023):1982-1993.

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