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您所在的位置:首頁 > 血液科醫(yī)學(xué)進展 > [ASCO2015]GATA-1, FOG-1和FLI-1對原發(fā)性血小板增多癥的調(diào)控

[ASCO2015]GATA-1, FOG-1和FLI-1對原發(fā)性血小板增多癥的調(diào)控

2015-06-03 22:53 閱讀:2609 來源:醫(yī)脈通 作者:林* 責(zé)任編輯:林夕
[導(dǎo)讀] GATA-1是GATA轉(zhuǎn)錄因子家族的始創(chuàng)成員,它對紅系和巨核細胞系的細胞成熟和分化是必要的。研究者證實原發(fā)性血小板增多癥(ET)患者骨髓的GATA-1表達升高,與JAK2V617F和CALR突變無關(guān)。

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

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

    【方法】

    研究者分析了GATA-1的表達水平與巨核細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本,其中17名JAK2突變(47%),4名CALR突變(11%),1名MPL突變(3%),14名無分子異常,與健康志愿者作對比。

    通過聚蔗糖分離豐富單核細胞碎片樣本。提取全部DNA并通過定時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。

    【結(jié)果】

    研究者證實了骨髓中獲取的數(shù)據(jù)——ET患者的GATA-1顯著上調(diào),而且GATA-1過表達與JAK2V617F和CALR突變無關(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.


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