GATA-1是GATA轉(zhuǎn)錄因子家族的始創(chuàng)成員，它對(duì)紅系和巨核細(xì)胞系的細(xì)胞成熟和分化是必要的。研究者證實(shí)原發(fā)性血小板增多癥（ET）患者骨髓的GATA-1表達(dá)升高，與JAK2V617F和CALR突變無(wú)關(guān)。

    GATA-1通過(guò)綁定DNA及其包含的蛋白伙伴（包括FOG-1和FLI-1轉(zhuǎn)錄因子）來(lái)協(xié)調(diào)細(xì)胞系特化。FOG-1對(duì)巨核細(xì)胞和紅系非常重要，而且它的表達(dá)大部分與GATA-1重疊。FLI-1是ETS家族成員，在巨核細(xì)胞祖細(xì)胞中高表達(dá)。GATA-1,FLI-1一起靶向這些基因，導(dǎo)致巨核細(xì)胞生成。

    【方法】

    研究者分析了GATA-1的表達(dá)水平與巨核細(xì)胞生成中相互作用轉(zhuǎn)錄因子、FOG-1和FLI-1的關(guān)系。從36名診斷為ET的患者中收集外周血標(biāo)本，其中17名JAK2突變（47%），4名CALR突變（11%），1名MPL突變（3%），14名無(wú)分子異常，與健康志愿者作對(duì)比。

    通過(guò)聚蔗糖分離豐富單核細(xì)胞碎片樣本。提取全部DNA并通過(guò)定時(shí)PCR分析，使用2-ΔΔCT 方法分析與管家基因GAPDH 相關(guān)的GATA-1,FOG-1和FLI-1表達(dá)。

    【結(jié)果】

    研究者證實(shí)了骨髓中獲取的數(shù)據(jù)——ET患者的GATA-1顯著上調(diào)，而且GATA-1過(guò)表達(dá)與JAK2V617F和CALR突變無(wú)關(guān)。但是，轉(zhuǎn)錄因子FOG-1和FLI-1受調(diào)控的方式似乎與ET患者中的GATA-1不同。

    【結(jié)論】

    這些結(jié)果表明GATA-1可特定解除原發(fā)性血小板增多癥的控制。

    英文摘要

    GATA-1, FOG-1, and FLI-1 regulation in essential thrombocythemia independently from JAK2 and CALRmutations.（Abstract No: 7020）Session Type: Poster Discussion Session

    Background:GATA-1 is the founding member of the GATA transc**tion factor family and it is essential for cell maturation and differentiation within the erythroid and megakaryocytic lineages. We and others have demonstrated that elevated GATA-1 expression is found in the bone marrow of Essential Thrombocythemia （ET）patients, independent of JAK2V617F and CALR mutations. GATA-1 is able to coordinate lineage specification through its ability to bind both DNA and protein partners that include; Friend of GATA （FOG-1） and the Friend leukemia integration 1 （FLI-1） transc**tion factors. FOG‐1 is vital for megakaryocyte and erythroid‐lineage commitment and its expression largely overlaps spatiotemporally with that of GATA-1. FLI-1 is an ETS family member that is expressed at high levels in megakaryocytic progenitors. In conjunction with GATA-1, FLI-1 targets those genes responsible for megakaryopoiesis.

    Methods:Following on from our earlier work we **yzed the expression levels of GATA-1in relation to its interacting transc**tion factors, FOG-1and FLI-1 in megakaryocyte development. Pe**heral blood specimens werecollected from 36 patients diagnosed with ET, 17 JAK2 mutated （47%）， 4 CALR（11%） mutated, 1 MPL mutated （3%） and 14 with no molecular abnormalities, and compared with a cohort of healthy volunteers. Samples were enriched for the mononuclear fraction by Ficoll separation. Total RNA was extracted and **yzedby Real Time PCR for GATA-1, FOG-1 and FLI-1 expression relative to the housekeeping gene GAPDH using the2-ΔΔCTmethod.

    Results:We confirmed the data obtained in bone marrow demonstrating that GATA-1 is significantly up-regulated in ET patients and that GATA-1 overexpression isindependent from JAK2V617F and CALR mutations. However, the transc**tionfactors FOG-1 and FLI-1 do not appear to be subject to the same regulatorycontrol in ET as that of GATA-1.

    Conclusions:These results suggest that GATA-1 is specifically deregulated in essential thrombocythemia.