Stavropoulou Chryssa, Georgakakos Vasileios N, Manola Kalliopi N, Pagoni Maria, Garofalaki Maria, Pantelias Gabriel E, Sambani Constantina
National Center for Scientific Research Demokritos, Athens, Greece.
Cancer Genet Cytogenet. 2008 Apr 1;182(1):50-5. doi: 10.1016/j.cancergencyto.2007.12.011.
Submicroscopic deletions of the PML-RARA fusion genes constitute rare rearrangements in acute promyelocytic leukemia (APL). We describe a rare case of APL carrying a novel complex translocation involving chromosomes 15, 17, and 18 associated with a submicroscopic deletion of the 5' part of the RARA gene, as evidenced by fluorescence in situ hybridization (FISH). A PML/RARA dual-fusion probe did not reveal the RARA-PML fusion signal on the der(17q), usually detected in the typical t(15;17). The RARA break-apart probe showed a deletion hybridization pattern with loss of the signal corresponding to the 5' portion of the RARA gene. Reverse transcriptase-polymerase chain reaction confirmed the absence of the fusion RARA-PML transcript. The patient achieved complete remission, but died during consolidation therapy, 2 months after diagnosis. To our knowledge, this is the first reported case of APL with a complex variant t(15;17) involving chromosome 18 at band q12 and one of the very rare described cases displaying a submicroscopic deletion of the RARA 5' region. Further cases are needed to delineate the incidence of submicroscopic deletions in APL and elucidate their prognostic impact.
PML-RARA融合基因的亚显微缺失在急性早幼粒细胞白血病（APL）中构成罕见的重排。我们描述了一例罕见的APL病例，其携带一种涉及15号、17号和18号染色体的新型复杂易位，并伴有RARA基因5'部分的亚显微缺失，荧光原位杂交（FISH）证实了这一点。PML/RARA双融合探针在der(17q)上未显示RARA-PML融合信号，而在典型的t(15;17)中通常可检测到该信号。RARA断裂分离探针显示出缺失杂交模式，对应于RARA基因5'部分的信号缺失。逆转录聚合酶链反应证实不存在融合的RARA-PML转录本。该患者实现了完全缓解，但在诊断后2个月的巩固治疗期间死亡。据我们所知，这是首例报道的APL病例，其具有涉及18号染色体q12带的复杂变异t(15;17)，也是极少数描述的显示RARA 5'区域亚显微缺失的病例之一。需要更多病例来确定APL中亚显微缺失的发生率，并阐明其预后影响。
