Role of MmTRA1 gene expression in acute myeloid leukemia cells

我们之前从小鼠致白血病Mm-P细胞cDNA文库中克隆了一个新的白血病发生相关基因MmTRA 1a，并且还从正常小鼠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。为探讨MmTRA 1b在髓系白血病中的作用，我们采用RT-PCR方法检测了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。

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.