Role of MmTRA1 gene expression in acute myeloid leukemia cells

我们之前从小鼠白血病Mm-P细胞cDNA文库中克隆了一个新的白血病发生相关基因MmTRA1a，并从正常小鼠cDNA文库中克隆了其正常对应基因MmTRA1b。MmTPAla是小鼠MmTRA1b的截断形式。我们从人单核细胞U937 cDNA文库中克隆了小鼠MmTRA1b的人正常对应体（MmTRA1b），发现其与磷脂合成酶1相同。全反式维甲酸（ATRA）可显著诱导急性早幼粒细胞白血病NB4和HT93细胞的粒细胞分化过程中MmTRA1b基因的表达。atra诱导的反义mmtra1b转染的NB4细胞分化明显受到抑制。另一方面，ATRA对mmtra1b转染的NB4细胞的诱导分化效果优于模拟转染的NB4细胞。在atra治疗的原发性急性早幼粒细胞白血病细胞的粒细胞分化过程中，MmTRA1b mRNA也被明显诱导。为了评估MmTRA1b表达在人髓性白血病中的作用，我们通过RT-PCR研究了81例急性髓性白血病（AML）患者中MmTRA1b转录本的相对水平。较高的MmTRA1b mRNA水平与AML患者较长的总生存期显著相关。

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.