Chillón M C, González M, García-Sanz R, Balanzategui A, González D, López-Pérez R, Mateos M V, Alaejos I, Rayón C, Arbeteta J, Hernández J M, Orfao A, San Miguel J
Hematology Service, Hospital Universitario de Salamanca and Centro de Investigacíon del Cancer (CIC), Universidad de Salamanca/CSIC, Salamanca, Spain.
Genes Chromosomes Cancer. 2000 Jan;27(1):35-43.
In the present article, two new types of PML/RARA junctions are described. Both were identified in diagnostic samples from two t(15;17)(q22;q21)-positive acute promyelocytic leukemia (APL) patients who failed to achieve complete remission. By using different sets of primers, reverse transcriptase polymerase chain reaction (RT-PCR) of PML/RARA junctions showed atypical larger bands compared with those generated from the three classical PML breakpoints already described. Sequence analysis of the fusion region of the amplified cDNAs allowed us to determine the specificity of these fragments in both patients. This analysis showed two new hybrid transcripts that were 53 and 306 base pairs (bp) longer than that expressed by the NB4 cell line (PML breakpoint within intron 6), and are the result of the direct joining of RARA exon 3 with PML exon 7a (patient 2) or the 5' portion of PML exon 7b (patient 1), respectively. In patient 1, RT-PCR analysis of the reciprocal RARA/PML junction showed a smaller transcript than that expected in bcr1 cases, while in patient 2 no amplified fragment was obtained. Cytogenetic analysis and/or fluorescence in situ hybridization (FISH) showed that both patients had the t(15;17) translocation. The clinical and hematological profiles expressed by the two patients carrying these unexpected types of PML/RARA rearrangement did not differ significantly from that commonly seen in other APLs with the exception of the poor outcome. Genes Chromosomes Cancer 27:35-43, 2000.
在本文中，描述了两种新型的PML/RARA融合点。这两种融合点均在两名t(15;17)(q22;q21)阳性急性早幼粒细胞白血病（APL）患者的诊断样本中被鉴定出来，这两名患者未能实现完全缓解。通过使用不同的引物组，PML/RARA融合点的逆转录聚合酶链反应（RT-PCR）显示出与已描述的三个经典PML断点所产生的条带相比非典型的更大条带。对扩增的cDNA融合区域进行序列分析使我们能够确定这两名患者中这些片段的特异性。该分析显示了两种新的杂交转录本，它们分别比NB4细胞系（内含子6内的PML断点）所表达的转录本长53和306个碱基对（bp），并且分别是RARA外显子3与PML外显子7a（患者2）或PML外显子7b的5'部分（患者1）直接连接的结果。在患者1中，对相互的RARA/PML融合点进行RT-PCR分析显示转录本比bcr1病例中预期的要小，而在患者2中未获得扩增片段。细胞遗传学分析和/或荧光原位杂交（FISH）显示两名患者均有t(15;17)易位。除了预后较差外，携带这些意外类型PML/RARA重排的两名患者所表现出的临床和血液学特征与其他APL中常见的特征没有显著差异。《基因、染色体与癌症》27:35 - 43，2000年。
