The cornerstone of management in patients with acute promyelocytic leukemia (APL) is early diagnosis and prompt initiation of treatment with an all-trans retinoic acid (ATRA)-based regimen. Identification of the t(15;17)(PML-RARA) chromosomal translocation through conventional cytogenetics fluorescence in-situ hybridization (FISH) or detection of the promyelocytic leukemia-retinoic acid receptor alpha (PML-RARα) fusion through RT-PCR represent the current standard of care for diagnosing APL. However, about 1–2% of patients with APL have a variant translocation involving other fusion partners with RARα besides PML. These patients present a unique diagnostic and clinical challenge in that conventional cytogenetics in addition to FISH and/or RT-PCR for PML-RARα may fail to identify these clinically relevant genetic lesions leading to an inappropriate diagnosis and treatment. We present two cases of patients who had APL with variant translocations whose bone marrow specimens were sent to the University of Michigan for enrollment in the MI-ONCOSEQ study (HUM00067928) after standard testing failed to identify PML-RARα or t(15;17) despite a phenotypic concern for this diagnosis. In these two patients, whole exome and transcriptome profiling via the MI-ONCOSEQ platform identified a PRKAR1A-RARα fusion in one patient and ZBTB16-RARα fusion in another patient. These cases illustrate the utility of whole exome and transcriptome profiling in diagnosing variant translocations in patients in whom there is a high clinical suspicion for APL based on hematopathology review.

急性早幼粒细胞白血病 (APL) 患者治疗的基石是早期诊断并迅速开始使用基于全反式视黄酸 (ATRA) 的方案进行治疗。通过常规细胞遗传学荧光原位杂交（FISH）鉴定t（15;17）（PML-RARA）染色体易位或通过RT-PCR检测早幼粒细胞白血病-视黄酸受体α（PML-RARα）融合代表目前诊断 APL 的护理标准。然而，大约 1-2% 的 APL 患者存在变异易位，涉及除PML之外的其他与RARα融合的伙伴。这些患者提出了独特的诊断和临床挑战，因为除了 FISH 和/或PML-RARα 的RT-PCR 外，常规细胞遗传学可能无法识别这些临床相关的遗传病变，从而导致不适当的诊断和治疗。我们介绍了两例 APL 变异易位患者，在标准测试未能识别PML-RARα或 t(15;17)后，他们的骨髓标本被送往密歇根大学参加 MI-ONCOSEQ 研究 (HUM00067928 )尽管对该诊断存在表型担忧。在这两名患者中，通过 MI-ONCOSEQ 平台的全外显子组和转录组分析确定了一名患者和ZBTB16-RARα的PRKAR1A-RARα融合融合在另一名患者身上。这些案例说明了全外显子组和转录组分析在根据血液病理学审查临床高度怀疑 APL 的患者中诊断变异易位的效用。