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您所在的位置:首页 > 血液科医学进展 > [ASCO2015]GATA-1, FOG-1和FLI-1对原发性血小板增多症的调控

[ASCO2015]GATA-1, FOG-1和FLI-1对原发性血小板增多症的调控

2015-06-03 22:53 阅读:1407 来源:医脉通 作者:林夕 责任编辑:林夕
[导读] GATA-1是GATA转录因子家族的始创成员,它对红系和巨核细胞系的细胞成熟和分化是必要的。研究者证实原发性血小板增多症(ET)患者骨髓的GATA-1表达升高,与JAK2V617F和CALR突变无关。

    GATA-1是GATA转录因子家族的始创成员,它对红系和巨核细胞系的细胞成熟和分化是必要的。研究者证实原发性血小板增多症(ET)患者骨髓的GATA-1表达升高,与JAK2V617F和CALR突变无关。

    GATA-1通过绑定DNA及其包含的蛋白伙伴(包括FOG-1和FLI-1转录因子)来协调细胞系特化。FOG-1对巨核细胞和红系非常重要,而且它的表达大部分与GATA-1重叠。FLI-1是ETS家族成员,在巨核细胞祖细胞中高表达。GATA-1,FLI-1一起靶向这些基因,导致巨核细胞生成。

    【方法】

    研究者分析了GATA-1的表达水平与巨核细胞生成中相互作用转录因子、FOG-1和FLI-1的关系。从36名诊断为ET的患者中收集外周血标本,其中17名JAK2突变(47%),4名CALR突变(11%),1名MPL突变(3%),14名无分子异常,与健康志愿者作对比。

    通过聚蔗糖分离丰富单核细胞碎片样本。提取全部DNA并通过定时PCR分析,使用2-ΔΔCT 方法分析与管家基因GAPDH 相关的GATA-1,FOG-1和FLI-1表达。

    【结果】

    研究者证实了骨髓中获取的数据——ET患者的GATA-1显著上调,而且GATA-1过表达与JAK2V617F和CALR突变无关。但是,转录因子FOG-1和FLI-1受调控的方式似乎与ET患者中的GATA-1不同。

    【结论】

    这些结果表明GATA-1可特定解除原发性血小板增多症的控制。

    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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