Torque Teno Mini Virus as a cause of childhood acute promyelocytic leukemia lacking PML/RARA fusion

We describe a case of a child affected by a relapsed PML/RARA-negative acute promyelocytic leukemia (APL) rescued by a combination of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) and subsequent HSCT. We provide evidence of the presence of a chimeric viral transcript generated through genomic integration of a Torque Teno Mini Virus sequence into RARA intron 2, the recurrent breakpoint of all chimeric RARA fusions found in APL. This generates an in-frame TTMV/RARA chimeric fusion that is highly expressed at disease diagnosis and relapse and fully cleared at remission achievement. Whole transcriptome sequencing of acute promyelocytic leukemia lacking PML/RARA fusion

本研究报道1例复发型PML/RARA阴性急性早幼粒细胞白血病（acute promyelocytic leukemia, APL）患者，该患者经全反式维甲酸（all-trans retinoic acid, ATRA）联合三氧化二砷（arsenic trioxide, ATO）治疗及后续造血干细胞移植（hematopoietic stem cell transplantation, HSCT）获得挽救性缓解。本研究证实，患者体内存在嵌合病毒转录本：其源于托罗坦诺迷你病毒（Torque Teno Mini Virus, TTMV）序列基因组整合至APL中所有RARA嵌合融合基因的复发性断裂位点——RARA基因内含子2区域。该整合可产生读码框完整的TTMV/RARA嵌合融合基因，该融合基因在疾病确诊及复发阶段均呈高表达，且在达到临床缓解后完全清除。针对缺乏PML/RARA融合基因的急性早幼粒细胞白血病的全转录组测序研究