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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:1135 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 transcription 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) transcription 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 transcription factors, FOG-1and FLI-1 in megakaryocyte development. Peripheral 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 transcriptionfactors 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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