Co-existence of IL7R high and SH2B3 low expression distinguishes a novel high-risk acute lymphoblastic leukemia with Ikaros dysfunction

Zheng Ge, Yan Gu, Lichan Xiao, Qi Han, Jianyong Li, Baoan Chen, James Yu, Yuka Imamura Kawasawa, Kimberly J. Payne, Sinisa Dovat, Chunhua Song

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Acute lymphoblastic leukemia (ALL) remains the leading cause of cancerrelated death in children and young adults. Compared to ALL in children, adult ALL has a much lower cure rate. Therefore, it is important to understand the molecular mechanisms underlying high-risk ALL and to develop therapeutic strategies that specifically target genes or pathways in ALL. Here, we explored the IL7R and SH2B3 expression in adult ALL and found that IL7R is significantly higher and Sh2B3 lower expressed in B-ALL compared to normal bone marrow control, and the IL7RhighSH2B3low is associated with high-risk factors, and with high relapse rate and low diseasefree survival rate in the patients. We also found that Ikaros deletion was associated with the IL7RhighSH2B3low expression pattern and Ikaros directly binds the IL7R and SH2B3 promoter, and suppresses IL7R and promotes SH2B3 expression. On the other hand, casein kinase inhibitor, which increases Ikaros function, inhibits IL7R and stimulates SH2B3 expression in an Ikaros dependent manner. Our data indicate that IL7RhighSH2B3low expression distinguishes a novel subset of high-risk B-ALL associated with Ikaros dysfunction, and also suggest the therapeutic potential for treatment that combines casein kinase inhibitor, as an Ikaros activator, with drugs that target the IL7R signaling pathway.

Original languageEnglish (US)
Pages (from-to)46014-46027
Number of pages14
JournalOncotarget
Volume7
Issue number29
DOIs
StatePublished - Jan 1 2016

All Science Journal Classification (ASJC) codes

  • Oncology

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