Analysis of CEV14-PDGFR chimeric gene

CEV14-PDGFR嵌合基因分析

• 批准号: 10670941
• 负责人: EMI Nobuhiko
• 金额: $ 2.05万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670941/
• 关键词: Leukemia; PDGFR; Chromosome; CEV14; Leukemia

Chromosomal translocations involving band 5q31-35 occur in several hematologic disorders. A clone with a t(5;14)(q33;q32) translocation appeared at the relapse phase in a patient with acute myelogenous leukemia who exhibited a sole chromosomal translocation, t(7;11) at initial diagnosis. Following the appearance of this clone, the leukemia progressed with marked eosnophilia, and combination chemotherapy was ineffective. Southern blot analysis revealed a rearrangement of the PDGFRβ gene at 5q33 which was not observed at initial diagnosis. This translocation resulted in a chimeric transcript fusing the platelet derived growth factor β receptor gene on 5q33 with a novel gene, CEV14, located at 14q32. Expression of the 5' region of the PDGFRβ cDNA, upstream of the breakpoint, was not detected. However, the 3' region of PDGFRβ which was transcribed as part of the CEV14-PDGFRβ fusion gene was detected. The novel gene, CEV14, includes a leucine zipper motif and putative thyroid hormone receptor interacting domain and is expressed in a wide range of tissues. The expression of a CEV14-PDGFRβ fusion gene in association with aggressive leukemia progression suggests that this protein has oncogenic potential.

涉及 5q31-35 条带的染色体易位发生在多种血液系统疾病中，具有 t(5;14)(q33;q32) 易位的克隆出现在急性髓性白血病患者的复发期，该患者表现出唯一的染色体易位 t(7)。 ;11) 在最初诊断时出现该克隆后，白血病进展并伴有明显的嗜酸粒细胞增多，并进行了联合化疗。 Southern 印迹分析显示 5q33 处的 PDGFRβ 基因发生重排，这种重排在最初诊断时未观察到，导致 5q33 上的血小板衍生生长因子 β 受体基因与位于 14q32 处的新基因 CEV14 融合的嵌合转录本。未检测到断点上游的 PDGFRβ cDNA 5' 区域的表达，但未检测到 PDGFRβ 的 3' 区域。检测到转录为 CEV14-PDGFRβ 融合基因的一部分。新基因 CEV14 包含亮氨酸拉链基序和假定的甲状腺激素受体相互作用结构域，并在多种组织中表达。与侵袭性白血病进展相关的融合基因表明该蛋白质具有致癌潜力。

项目成果

Abe Akihiro: "Polybrene increases the efficiency of gene transfer by lipofection" Gene Therapy. in press.

Abe Akihiro：“Polybrene 通过脂转染提高了基因转移的效率”基因治疗。

Yoshie KUNO: "AN ATYPICAL MYELODYSPLASTIC SYNOROME WITH t(9;12)(922;p12)AND TEL GENE REARRENGEMENT"British Journal of Haematology. 106. 570-571 (1999)

Yoshie KUNO：“伴有 t(9;12)(922;p12) 和 TEL 基因重排的非典型骨髓增生异常综合征”英国血液学杂志。

Akio Kohno: "Semliki Forest Vinis based DNA expression vector : Transient protein production followed by necro :" Gene Therapy. 5. 415-418 (1998)

Akio Kohno：“基于 Semliki Forest Vinis 的 DNA 表达载体：瞬时蛋白质生产，然后是坏死：”基因治疗。

KUNO Yoshie, ABE Akihiko, EMI Nobuhiko, IIDA Minako, YAMAMORI Toshiharu, TANIMOTO Mitsue, SAITO Hidehiko: "AN ATYPICAL MYELODYSPLASTIC SYNDROME WITH t(9;129)(q22;p12) AND TEL GENE REARRANGEMENT"British Journal of Haematology. 106. 570-571 (1999)

KUNO Yoshie、ABE Akihiko、EMI Nobuhiko、IIDA Minako、YAMAMORI Toshiharu、TANIMOTO Mitsue、SAITO Hidehiko：“一种伴有 t(9;129)(q22;p12) 和 TEL 基因重排的非典型骨髓增生异常综合征”英国血液学杂志。

Nobubiko EMI: "CD4-and CD56-positive T-cell line,MTA,established frome natural killer-like T-cell leukemia/lymphoma."International Journal of HEMATOLOGY. 69. 180-185 (1999)

Nobubiko EMI：“CD4 和 CD56 阳性 T 细胞系，MTA，从自然杀伤样 T 细胞白血病/淋巴瘤中建立。”国际血液学杂志。