Role of MmTRA1 gene expression in acute myeloid leukemia cells

MmTRA1基因表达在急性髓系白血病细胞中的作用

• 批准号: 13671090
• 负责人: KASUKABE Takashi
• 金额: $ 2.24万
• 依托单位: Research Institute for Clinical Oncology, Saitama Cancer Center
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671090/
• 关键词: MmTRA1 gene; phospholipid scramblase 1; oncogene; leukemia; differentiation; prognostic factor; granulocytes; リン脂質スクランブレース; 白血病細胞; proline-rich領域; 細胞膜

We previously cloned a new leukemogenesis-associated gene MmTRA1a from a mouse leukemogenic Mm-P cell cDNA library and also cloned its normal counterpart MmTRA1b from a normal mouse cDNA library. The MmTPAla is a truncated form of mouse MmTRA1b. We cloned human normal counterpart (MmTRA1b) of the mouse MmTRA1b from a human monocytic U937 cDNA library and found that it was identical to the phospholipid scramblase 1. Expression of MmTRA1b gene was markedly induced during granulocytic differentiation of acute promyelocytic leukemia NB4 and HT93 cells by all-trans retinoic acid (ATRA). ATRA-induced differentiation of antisense MmTRA1b-transfected NB4 cells was significantly suppressed. On the other hand, ATRA induced the differentiation of MmTRA1b-transfected NB4 cells more efficiently than that of mock-transfected cells. MmTRA1b mRNA also was clearly induced in ATRA-treated primary acute promyelocytic leukemia cells during granulocytic differentiation. To evaluate the role of MmTRA1b expression in human myeloid leukemia, we investigated the relative levels of MmTRA1b transcripts in 81 patients with acute myelogenous leukemia (AML) by RT-PCR. Higher MmTRA1b mRNA levels were associated with significantly longer overall survival in AML.

我们以前从小鼠白血病Mm-P细胞cDNA文库中克隆了一个新的白血病相关基因MmTRA 1a，并从正常小鼠cDNA文库中克隆了其正常对应基因MmTRA 1b。MmTPAla是小鼠MmTRA 1b的截短形式。我们从人单核细胞U937 cDNA文库中克隆了小鼠MmTRA 1b的人正常对应物（MmTRA 1b），发现它与磷脂扰码酶1相同。全反式维甲酸（ATRA）诱导急性早幼粒细胞白血病NB 4和HT 93细胞粒系分化过程中，MmTRA 1b基因表达显著增加。反义MmTRA 1b转染的NB 4细胞的ATRA诱导的分化被显著抑制。另一方面，ATRA诱导分化的MmTRA 1b转染NB 4细胞比模拟转染细胞更有效。在ATRA处理的原代急性早幼粒细胞白血病细胞粒细胞分化过程中，MmTRA 1b mRNA也明显诱导。为了评估MmTRA 1b表达在人类髓系白血病中的作用，我们通过RT-PCR研究了81例急性髓系白血病（AML）患者MmTRA 1b转录本的相对水平。较高的MmTRA 1b mRNA水平与AML患者的总生存期显著延长相关。

项目成果

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Okabe-Kado J: "Physiological and pathological relevance of extracellular NM23/NDP kinases."J.Bioener.Biomemb.. 35. 89-93 (2003)

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Yokoyama A: "MmTRA1b/phospholipid scramblase 1 gene expression is a new prognostic factor for acute myelogenous leukemia."Leukemia Res.. 28. 149-157 (2004)

Yokoyama A：“MmTRA1b/磷脂扰乱酶 1 基因表达是急性髓性白血病的新预后因素。”Leukemia Res.. 28. 149-157 (2004)

Nakamaki T: "Role of MmTRA1b/phospholipid scramblase 1 gene expression in the induction of differentiation of human myeloid leukemia cells into granulocytes."Exp.Hematol.. 30. 421-429 (2002)

Nakamaki T：“MmTRA1b/磷脂扰乱酶 1 基因表达在诱导人骨髓性白血病细胞分化为粒细胞中的作用。”Exp.Hematol.. 30. 421-429 (2002)

Okabe-Kado, J.: "Expression oteell surface NM23 proteins of human leukemia cell lines of various cellular lineage and differentiation stages"Leukemia Res.. 30. 569-576 (2002)

Okabe-Kado，J.：“各种细胞谱系和分化阶段的人白血病细胞系的表面 NM23 蛋白的表达”Leukemia Res.. 30. 569-576 (2002)