Russell M, List A, Greenberg P, Woodward S, Glinsmann B, Parganas E, Ihle J, Taetle R
Department of Medicine, University of Arizona, Tucson.
Blood. 1994 Aug 15;84(4):1243-8.
The EVI1 gene encodes a zinc-finger, DNA-binding protein originally described as the transforming gene associated with a common ecotropic viral insertion site in myeloid leukemias. Previous studies demonstrated EVI1 expression in human leukemias in cases with 3q26 translocations, but not in normal blood or bone marrow. These studies also suggested an association between EVI1 expression and chromosome 7 deletion (del). Because of this association, we examined expression of EVI1 using RNA polymerase chain reaction (PCR) in patients with myelodysplastic syndromes (MDS) and acute leukemia with and without 3q26 translocations. EVI1 RNA was expressed in 29% of 34 (95% confidence interval, 20% to 50%) patients with the MDS subtypes refractory anemia (RA), refractory anemia with excess blasts (RAEB), or refractory anemia with excess blasts in transformation (RAEB-T). The vast majority of these cases occurred in patients with RAEB and RAEB-T. EVI1 expression was not detected in patients with chronic myelomonocytic leukemia (CMML), normal bone marrow or cord blood, or a variety of other hematologic malignancies. EVI1 RNA was detected in three of 18 patients with acute myelogenous leukemia (AML) and in two of four patients with acute promyelocytic leukemia (APL). Karyotypes showed that only one AML patient had karyotype 3q26 abnormalities, indicating that EVI1 expression is associated with cases that do not have structural abnormalities involving chromosome 3q26. These studies document for the first time the abnormal expression of EVI1 RNA by patients with MDS, and suggest an important role for EVI1 in the pathogenesis or progression of some myeloid malignancies.
EVI1基因编码一种锌指DNA结合蛋白，最初被描述为与髓系白血病中常见嗜亲性病毒插入位点相关的转化基因。先前的研究表明，在3q26易位的人类白血病病例中可检测到EVI1表达，但在正常血液或骨髓中未检测到。这些研究还提示EVI1表达与7号染色体缺失（del）之间存在关联。基于这种关联，我们运用RNA聚合酶链反应（PCR）检测了伴有或不伴有3q26易位的骨髓增生异常综合征（MDS）和急性白血病患者中EVI1的表达情况。在34例患有难治性贫血（RA）、难治性贫血伴原始细胞增多（RAEB）或难治性贫血伴原始细胞增多转变型（RAEB-T）等MDS亚型的患者中，29%（95%置信区间为20%至50%）的患者表达EVI1 RNA。这些病例绝大多数发生在RAEB和RAEB-T患者中。在慢性粒单核细胞白血病（CMML）患者、正常骨髓或脐血以及其他多种血液系统恶性肿瘤患者中未检测到EVI1表达。在18例急性髓系白血病（AML）患者中有3例检测到EVI1 RNA，在4例急性早幼粒细胞白血病（APL）患者中有2例检测到EVI1 RNA。核型分析显示，只有1例AML患者存在3q26核型异常，这表明EVI1表达与不涉及3q26染色体结构异常的病例相关。这些研究首次证实了MDS患者中EVI1 RNA的异常表达，并提示EVI1在某些髓系恶性肿瘤的发病机制或进展中发挥重要作用。
