Acute promyelocytic leukemia (APL) is characterized by the presence of promyelocytic leukemia-retinoic acid receptor α (PML-RARα) fusion gene, which is formed following the specific chromosomal translocation t(15;17)(q22;q21). However, cases with PML-RARα generated by occult t(15;17) which are negative by both cytogenetics and fluorescence in situ hybridization (FISH), are difficult to diagnose, leading to impaired treatment effectiveness. In the present study, we reported a case of a 66-year-old male patient, and bone marrow morphology, flow cytometry and cytogenetics did not support the diagnosis of APL. Molecular techniques, such as reverse-transcription polymerase chain reaction (RT-PCR), showed the existence of a cryptic PML-RARα fusion gene, and sequence analysis revealed a new variable isoform. Hotspot gene mutation analysis showed a biallelic CEBPA mutation. He received IA chemotherapy and all-trans retinoic acid (ATRA) treatment, and finally achieved complete remission. This case report provided valuable insights into the relevance of the correct identification of atypical PML-RARα fusion gene and biallelic CEBPA mutation. Moreover, combination of IA chemotherapy and ATRA treatment suggested a good clinical effect in this atypical PML-RARα.

中文翻译：

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在急性早幼粒细胞白血病病例中鉴定出没有 t(15;17) 和双等位基因 CEBPA 突变的新隐性 PML-RARα 融合基因：仅通过 RT-PCR 检测但未通过细胞遗传学和 FISH 检测到的病例。

急性早幼粒细胞白血病（APL）的特征是存在早幼粒细胞白血病-视黄酸受体α（PML-RARα）融合基因，该基因在特定染色体易位t(15;17)(q22;q21)后形成。然而，由细胞遗传学和荧光原位杂交 (FISH) 均呈阴性的隐匿性 t(15;17) 产生的 PML-RARα 病例难以诊断，导致治疗效果受损。在本研究中，我们报告了一例 66 岁男性患者，骨髓形态学、流式细胞术和细胞遗传学不支持 APL 的诊断。分子技术，如逆转录聚合酶链反应 (RT-PCR)，表明存在一个隐秘的 PML-RARα 融合基因，序列分析揭示了一种新的可变异构体。热点基因突变分析显示双等位基因 CEBPA 突变。他接受了IA化疗和全反式维甲酸（ATRA）治疗，最终达到完全缓解。该病例报告为正确识别非典型 PML-RARα 融合基因和双等位基因 CEBPA 突变的相关性提供了宝贵的见解。此外，IA 化疗和 ATRA 治疗的组合表明这种非典型 PML-RARα 具有良好的临床效果。