Ikaros: Exploiting and targeting the hematopoietic stem cell niche in B-progenitor acute lymphoblastic leukemia

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• 作者：Michelle L. Churchman ; Charles G. Mullighan ; ^{charles.mullighan@stjude.org}
• 刊名：Experimental Hematology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：46
• 期：Complete
• 页码：1-8
• 全文大小：1102 K
• 卷排序：46

文摘

IKZF1 (IKAROS) deletions and mutations are a hallmark of high risk B-progenitor ALL, and are associated with poor outcome. Genetic alteration of IKZF1 result in loss of IKAROS activity, with acquisition of a hematopoietic stem cell-like phenotype, and induction of adhesion molecule expression and signaling. Mislocalization of leukemic cells in the bone marrow hematopoietic niche is characteristic of IKZF1-mutated B-ALL. IKZF1 alterations create a therapeutic vulnerability by upregulating rexinoid receptor expression that can be targeted with rexinoid agonists. Rexinoid agonists and focal adhesion kinase inhibitors synergize with tyrosine kinase inhibitors in IKZF1-mutated ALL.