Objective: To investigate the genetic screening methods for cryptic acute promyelocytic leukemia (APL) to further explore its clinical prognosis. Methods: From June 2016 to November 2018, we collected 373 newly diagnosed APL cases. The patients were retrospected by the results of PML-RARα detections both by RT-PCR and i-FISH, those who harbored positive PML-RARα detection by RT-PCR and negative by i-FISH were chosen. Metaphase FISH and Sanger sequencing were further performed to verify these results. Results: A total of 7 cryptic APL cases were discovered. These cases had tiny fragment of RARα inserted into PML in chromosome 15, formed ins (15;17) . The 7 cryptic APL cases had no PML-RARα gene subtype specificity, involving 5 cases in L subtype, 1 case in S subtype and 1 case in V subtype respectively. After the treatment of retinoic acid and arsenic or anthracyclines, 6 cases achieved complete remission, 1 case died of intracranial hemorrhage on the 6th day of therapy. Conclusion: The size and covering position of PML-RARα probe should be taken into account when PML-RARα was performed by FISH on APL patients. Furthermore, combination with Metaphase FISH could improve the recognition of cryptic APL. There were no differences between the cryptic and common APL patients in terms of clinical features and treatment choices. Cryptic APL patients also had a good response to the therapy of retinoic acid and arsenic or anthracyclines.
目的： 探讨伴ins（15;17）隐匿型急性早幼粒细胞白血病（APL）的遗传学检测方法及其临床预后。 方法： 收集2016年6月至2018年11月收治的373例初诊APL病例，筛选出PML-RARα检测RT-PCR阳性、间期FISH阴性的APL患者进行回顾检测分析，采用中期FISH和Sanger测序进一步验证。 结果： 共发现7例隐匿型APL患者，这7例患者15号染色体上分别插入了小的RARα片段，形成ins（15；17）。7例患者中L亚型5例，S亚型1例，V亚型1例。经全反式维甲酸（ATRA）和亚砷酸（ATO）或蒽环类等化疗药物联合化疗后，有6例患者完全缓解，1例患者化疗第6天死于颅内出血。 结论： APL进行FISH检测时应考虑探针大小及覆盖位置，联合中期FISH可提高隐匿型APL检出率。伴ins（15;17）隐匿型APL患者临床特征及治疗方案与经典型APL无差异，ATRA与ATO或蒽环类等联合化疗有效。.
Keywords: Cryptic insertion translocation; Leukemia, promyelocytic, acute; Metaphase fluorescence in situ hybridization.