Borrow J, Shipley J, Howe K, Kiely F, Goddard A, Sheer D, Srivastava A, Antony A C, Fioretos T, Mitelman F
Somatic Cell Genetics Laboratory, Imperial Cancer Research Fund, London, UK.
Genes Chromosomes Cancer. 1994 Apr;9(4):234-43. doi: 10.1002/gcc.2870090403.
The primary cytogenetic abnormality in acute promyelocytic leukemia (APL; FAB M3) is a reciprocal translocation, t(15;17)(q22;q12), which serves to fuse the PML gene on chromosome 15 to the retinoic acid receptor alpha (RARA) gene on chromosome 17. A PML-RARA fusion message transcribed from the der(15) is thought to mediate leukemogenesis. Two APL patients with simple variants of this translocation, t(3;15)(q21;q22) and t(X;15)(p11;q22), have previously been reported who lack cytogenetic involvement of chromosome 17, although their breakpoint positions on chromosome 15 still suggest the involvement of the PML gene. Here we report on a combined analysis by molecular genetics and in situ hybridization of these two patients, in which we wanted to determine whether the PML gene has alternative fusion partners or whether cryptic rearrangement of the RARA locus has occurred instead. A cryptic involvement of RARA was demonstrated in both patients by a combination of Southern analysis, reverse transcription coupled to PCR (RT-PCR), and fluorescence in situ hybridization. The results indicate an absolute requirement for the rearrangement of the RARA gene in the pathogenesis of APL and underline the importance of RARA during normal myeloid differentiation.
急性早幼粒细胞白血病（APL；FAB M3）的主要细胞遗传学异常是一种相互易位，即t(15;17)(q22;q12)，它使15号染色体上的PML基因与17号染色体上的维甲酸受体α（RARA）基因融合。从der(15)转录的PML-RARA融合信息被认为介导了白血病的发生。此前曾报道过两名具有这种易位简单变体t(3;15)(q21;q22)和t(X;15)(p11;q22)的APL患者，他们缺乏17号染色体的细胞遗传学受累情况，尽管他们在15号染色体上的断点位置仍提示PML基因受累。在此，我们报告了对这两名患者进行的分子遗传学和原位杂交联合分析，我们想确定PML基因是否有其他融合伙伴，或者是否发生了RARA基因座的隐匿性重排。通过Southern分析、逆转录偶联PCR（RT-PCR）和荧光原位杂交相结合的方法，在两名患者中均证实了RARA的隐匿性受累。结果表明RARA基因重排在APL发病机制中是绝对必要的，并强调了RARA在正常髓系分化过程中的重要性。
