Venci Anna, Mazza Rita, Spinelli Orietta, Di Schiena Luciana, Bettio Daniela
Cytogenetic and Medical Genetic Laboratory, Operative Unit of Clinical Investigations, Humanitas Clinical and Research Center, I-20089 Milan, Italy.
Operative Unit of Medical Oncology and Hematology, Humanitas Clinical and Research Center, I-20089 Milan, Italy.
Oncol Lett. 2017 Jun;13(6):4180-4184. doi: 10.3892/ol.2017.5979. Epub 2017 Apr 3.
Acute promyelocytic leukemia is a myeloid disorder that is characterized by the specific t(15;17) variant in ~98% of cases. The typical hypergranular and microgranular or hypogranular types exist, and are frequently associated with disseminated intravascular coagulopathy. Rare cases of promyelocytic leukemia-retinoic acid receptor α (PML-RARA) fusion without the reciprocal RARA-PML have been reported in cytogenetically normal samples. Conversely, fluorescence hybridization (FISH) analysis has revealed a cryptic insertion of the RARA gene into the PML gene on chromosome 15. The current study reports a unique case with a normal karyotype and molecular evidence of the PML-RARA short isoform 3-fusion transcript, with FISH analysis revealing two fusion signals on the two copies of chromosome 15, but absence of the reciprocal on the two copies of chromosome 17. This finding raised the hypothesis of chromosome 15 uniparental isodysomy as consequence of normal chromosome 15 loss and duplication of the rearranged chromosome, as supported by polymorphic loci molecular analysis. The clinical, cytogenetic and molecular characterization of this case are presented and discussed in the present study.
急性早幼粒细胞白血病是一种髓系疾病，约98%的病例具有特异性的t(15;17)变异。存在典型的高颗粒型、微颗粒型或低颗粒型，且常与弥散性血管内凝血相关。在细胞遗传学正常的样本中，曾报道过罕见的早幼粒细胞白血病-维甲酸受体α（PML-RARA）融合而无反向RARA-PML的病例。相反，荧光原位杂交（FISH）分析显示RARA基因隐匿插入15号染色体上的PML基因。本研究报告了1例核型正常且有PML-RARA短异构体3融合转录本分子证据的独特病例，FISH分析显示在15号染色体的两个拷贝上有两个融合信号，但在17号染色体的两个拷贝上没有反向信号。这一发现提出了15号染色体单亲等臂染色体的假说，即15号正常染色体丢失和重排染色体复制的结果，多态性位点分子分析支持这一假说。本研究对该病例的临床、细胞遗传学和分子特征进行了介绍和讨论。
