FUSION BETWEEN A NOVEL KRUPPEL-LIKE ZINC FINGER GENE AND THE RETINOIC ACID RECEPTOR-ALPHA LOCUS DUE TO A VARIANT T(11,17) TRANSLOCATION ASSOCIATED WITH ACUTE PROMYELOCYTIC LEUKEMIA
FUSION BETWEEN A NOVEL KRUPPEL-LIKE ZINC FINGER GENE AND THE RETINOIC ACID RECEPTOR-ALPHA LOCUS DUE TO A VARIANT T(11,17) TRANSLOCATION ASSOCIATED WITH ACUTE PROMYELOCYTIC LEUKEMIA
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DOI：
10.1002/j.1460-2075.1993.tb05757.x
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发表时间：
1993-03-01
期刊：
影响因子：
11.4
通讯作者：
ZELENT, A
中科院分区：
文献类型：
--
作者：
CHEN, Z;BRAND, NJ;ZELENT, A
我们已经确定了一个独特的情况下，急性早幼粒细胞白血病（APL）的t（11;17）相互染色体易位涉及维甲酸受体α（RAR α）和以前未知的锌指基因。作为这种易位的结果，含有新基因编码序列的mRNA从重排的等位基因中表达，所述新基因编码序列在RAR α B区的上游或两种主要RAR α同种型的独特A1和A2区的下游框内融合。上述基因，我们称之为PLZF（用于早幼粒细胞白血病锌指），编码一种潜在的转录因子，其含有9个与果蝇间隙基因Kruppel相关的锌林格基序，并表达为至少两种在编码蛋白质的N-末端区域的序列上不同的同种型。在造血系统中，PLZF mRNA在骨髓、早期髓样细胞和外周血单核细胞中检测到，但在淋巴细胞系或组织中未检测到。此外，在NB-4和HL-60早幼粒细胞系中，PLZF mRNA水平在视黄酸诱导的粒细胞分化中下调，而在成熟粒细胞中则非常低。我们的研究结果首次证明了涉及RAR α基因的变异染色体易位与APL的关联，进一步暗示了RAR α在白血病发生中的作用，也表明PLZF以及视黄酸及其受体在骨髓成熟中的重要作用。
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 (RARalpha) 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 RARalpha B region or downstream from the unique A1 and A2 regions of the two major RARa 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 ringer motifs related to the Drosophila gap gene Kruppel 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 tines 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 tow in mature granulocytes. Our results demonstrate for the first time the association of a variant chromosomal translocation involving the RARalpha gene with APL, further implicating the RARalpha in leukaemogenesis and also suggesting an important role for PLZF as well as retinoic acid and its receptors in myeloid maturation.