Chen Z, Brand N J, Chen A, Chen S J, Tong J H, Wang Z Y, Waxman S, Zelent A
Shanghai Institute of Haematology, Rui-Jin Hospital, Shanghai Second Medical University, China.
EMBO J. 1993 Mar;12(3):1161-7. doi: 10.1002/j.1460-2075.1993.tb05757.x.
We have identified a unique case of acute promyelocytic leukaemia (APL) with a t(11;17) reciprocal chromosomal translocation involving the retinoic acid receptor alpha (RAR alpha) and a previously uncharacterized zinc finger gene. As a result of this translocation, mRNAs containing the coding sequences of the new gene, fused in-frame either upstream of the RAR alpha B region or downstream from the unique A1 and A2 regions of the two major RAR alpha isoforms, are expressed from the rearranged alleles. The above gene, which we have termed PLZF (for promyelocytic leukaemia zinc finger), encodes a potential transcription factor containing nine zinc finger motifs related to the Drosophila gap gene Krüppel and is expressed as at least two isoforms which differ in the sequences encoding the N-terminal region of the protein. Within the haematopoietic system the PLZF mRNAs were detected in the bone marrow, early myeloid cell lines and peripheral blood mononuclear cells, but not in lymphoid cell lines or tissues. In addition, the PLZF mRNA levels were down-regulated in NB-4 and HL-60 promyelocytic cell lines in response to retinoic acid-induced granulocytic differentiation and were very low in mature granulocytes. Our results demonstrate for the first time the association of a variant chromosomal translocation involving the RAR alpha gene with APL, further implicating the RAR alpha in leukaemogenesis and also suggesting an important role for PLZF as well as retinoic acid and its receptors in myeloid maturation.
我们鉴定出一例独特的急性早幼粒细胞白血病（APL），其存在t(11;17)相互染色体易位，涉及维甲酸受体α（RARα）和一个此前未被鉴定的锌指基因。由于这种易位，包含新基因编码序列的mRNA从重排的等位基因表达，这些mRNA在RARα B区域上游或两种主要RARα异构体独特的A1和A2区域下游与框架内融合。我们将上述基因命名为PLZF（早幼粒细胞白血病锌指），它编码一种潜在的转录因子，含有九个与果蝇缺口基因Krüppel相关的锌指基序，并表达为至少两种异构体，它们在编码蛋白质N端区域的序列上有所不同。在造血系统中，PLZF mRNA在骨髓、早期髓系细胞系和外周血单个核细胞中被检测到，但在淋巴系细胞系或组织中未被检测到。此外，在NB-4和HL-60早幼粒细胞系中，PLZF mRNA水平在维甲酸诱导的粒细胞分化过程中下调，在成熟粒细胞中非常低。我们的结果首次证明了涉及RARα基因的变异染色体易位与APL的关联，进一步表明RARα参与白血病发生，同时也提示PLZF以及维甲酸及其受体在髓系成熟中起重要作用。
