Impaired function of the Ikaros (IKZF1) protein is associated with the development of high-risk B-cell precursor acute lymphoblastic leukemia (B-ALL).
IKZF1蛋白功能受損與高位前B細(xì)胞急性B淋巴細(xì)胞白血病高度相關(guān)
?The mechanisms of Ikaros tumor suppressor activity in leukemia are unknown. Ikaros binds to the upstream regulatory elements of its target genes and regulates their transcription via chromatin remodeling.?
IKZF1抑制腫瘤的活性在白血病中機制尚不清楚颈抚。IKZF1結(jié)合在靶基因上游的調(diào)控元件上鸦致，通過染色體重塑來調(diào)節(jié)他們的轉(zhuǎn)錄疲吸。
Here, we report that Ikaros represses transcription of the histone H3K4 demethylase, JARID1B (KDM5B).
我們在這里發(fā)現(xiàn)了IKZF1抑制組蛋白H3K4脫甲基酶憋沿，JARID1B的轉(zhuǎn)錄
?Transcriptional repression of JARID1B is associated with increased global levels of H3K4 trimethylation.?
JARID1B的轉(zhuǎn)錄抑制與H3K4的甲基化水平相關(guān)
Ikaros-mediated repression of JARID1B is dependent on the activity of the histone deacetylase, HDAC1, which binds to the upstream regulatory element of JARID1B in complex with Ikaros.?
IKZF1抑制JARID1B依賴于HDAC1塑悼，組蛋白脫乙酰酶的活性锻狗，HDAC1與IKZF1組合成復(fù)合物共同結(jié)合到JARID1B的上游調(diào)節(jié)元件上
In leukemia, JARID1B is overexpressed, and its inhibition results in cellular growth arrest. Ikaros-mediated repression of JARID1B in leukemia is impaired by pro-oncogenic casein kinase 2 (CK2).?
在白血病中，JARID1B是過表達(dá)的狰住，抑制JARID1B的表達(dá)導(dǎo)致細(xì)胞生長停滯张吉。IKZF1在白血病中抑制JARID1B的表達(dá)這一過程會被原癌酪蛋白激酶中斷。
Inhibition of CK2 results in increased binding of the Ikaros-HDAC1 complex to the promoter of JARID1B, with increased formation of trimethylated histone H3 lysine 27 and decreased histone H3 Lys-9 acetylation.?
抑制CK2會增加IKZF1-HDAC1復(fù)合物在JARID1B啟動子區(qū)域的結(jié)合催植，三甲基化組蛋白H3賴氨酸27的形成增加肮蛹，減少組蛋白H3-LYS-9的乙酰化
In cases of high-risk B-ALL that carry deletion of one Ikaros (IKZF1) allele, targeted inhibition of CK2 restores Ikaros binding to the JARID1B promoter and repression of JARID1B.?
在一例攜帶IKZF1雜合缺失的高風(fēng)險B-ALL的病例中创南，CK2的靶向抑制會恢復(fù)IKZF1與JARID1B啟動子的結(jié)合伦忠，并抑制JARID1B
In summary, the presented data suggest a mechanism through which Ikaros and HDAC1 regulate the epigenetic signature in leukemia: via regulation of JARID1B transcription. The presented data identify JARID1B as a novel therapeutic target in B-ALL and provide a rationale for the use of CK2 inhibitors in the treatment of high-risk B-ALL.
綜上所述，目前的數(shù)據(jù)發(fā)現(xiàn)了一種通過IKZF1與HDAC1調(diào)控白血病表觀遺傳特征的機制：調(diào)控JARID1B的轉(zhuǎn)錄「逭蓿現(xiàn)有的數(shù)據(jù)證明JARID1B是B-ALL的一個新的治療靶點昆码，為利用CK2抑制劑治療高風(fēng)險B-ALL提供了理論依據(jù)
