Aberrant expression of microRNA in polycythemia vera
Aberrant expression of microRNA in polycythemia vera
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DOI：
10.3324/haematol.12706
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发表时间：
2008-07-01
期刊：
影响因子：
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通讯作者：
Prchal, Josef T.
中科院分区：
文献类型：
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作者：
Bruchova, Hana;Merkerova, Michaela;Prchal, Josef T.
背景真性红细胞增多症是一种克隆性造血干细胞疾病，在>95%的患者中观察到JAK 2 V617 F突变，但一个尚未确定的过程似乎启动了造血的克隆性扩增。由于microRNA调节造血分化，我们假设，表达失调的microRNA可能有助于真性红细胞增多症的病理生理学。设计和MethodsWe进行了基因表达谱在5例真性红细胞增多症患者和5个控制使用CombiMatrix MicroRNA定制阵列。ANOVA鉴定了真性红细胞增多症中失调的microDRNA，并通过定量逆转录聚合酶链反应在更大的样本组中研究了它们的表达。这些microRNA的表达也在其他骨髓增生性疾病中进行了分析。结果我们观察到在真性红细胞增多症粒细胞中let-7a的下调和miR-182的上调，在真性红细胞增多症单核细胞中miR-143、miR-145和miR-223的上调，在真性红细胞增多症血小板中miR-26 b的上调，以及miR-30 b的下调，真性红细胞增多症网织红细胞中的miR-30 c和miR-150。JAK 2 V617 F频率与miR-143表达正相关，与let-7a、miR-30 c、miR-342和miR-150负相关。确定预测的靶基因的转录水平，并在来自骨髓增生性疾病患者的所有粒细胞和真性红细胞增多症网织红细胞中检测到IRAK 2的过表达。异常高的HMGA 2 microRNA被发现在骨髓纤维化granulocyte.ConclusionsOur研究表明，外周血细胞与真性红细胞增多症患者的microRNA签名不同于那些控制。我们发现microRNA表达异常强调了真性红细胞增多症分子基础的复杂性。
BackgroundPolycythemia vera is a clonal hematopoietic stem cell disorder in which the JAK2 V617F mutation is observed in >95% of patients, but an as yet unidentified process appears to initiate the clonal expansion of hematopoiesis. Because microRNA regulate hematopoietic differentiation, we hypothesized that dysregulated expression of microRNA may contribute to the pathophysiology of polycythemia vera.Design and MethodsWe performed gene expression profiling in five patients with polycythemia vera and in five controls using CombiMatrix MicroRNA CustomArray. ANOVA identified deregulated microDRNA in polycythemia vera, and their expression was studied in a larger set of samples by quantitative reverse transcriptase polymerase chain reaction. The expression of these microRNA was also analyzed in other myeloproliferative disorders.ResultsWe observed down-regulation of let-7a and up-regulation of miR-182 in polycythemia vera granulocytes, up-regulation of miR-143, miR-145 and miR-223 in polycythemia vera mononuclear cells, up-regulation of miR-26b in polycythemia vera platelets, and down-regulation of miR-30b, miR-30c and miR-150 in polycythemia vera reticulocytes. JAK2 V617F frequency was positively correlated with miR-143 expression and inversely correlated with let-7a, miR-30c, miR-342 and miR-150. Transcript level of predicted target genes was determined, and overexpression of IRAK2 was detected in all granulocytes from patients with myeloproliferative disorders and in polycythemia vera reticulocytes. Abnormally high HMGA2 microRNA was found in myelofibrosis granulocytes.ConclusionsOur study demonstrates that peripheral blood cells from patients with polycythemia vera have microRNA signatures distinct from those of controls. Our findings of aberrant microRNA expression underline the complexity of the molecular basis of polycythemia vera.