Acute WT1-positive promyelocytic leukemia with hypogranular variant morphology, bcr-3 isoform of PML-RARα and Flt3-ITD mutation: a rare case report

ABSTRACT CONTEXT: Acute promyelocytic leukemia (APL) accounts for 8% to 10% of cases of acute myeloid leukemia (AML). Remission in cases of high-risk APL is still difficult to achieve, and relapses occur readily. CASE REPORT: Here, we describe a case of APL with high white blood cell counts in blood tests and hypogranular variant morphology in bone marrow, together with fms-like tyrosine kinase-3 with internal tandem duplication mutations (FLT3-ITD), and bcr-3 isoform of PML-RARα. Most importantly, we detected high level of Wilms’ tumor gene (WT1) in marrow blasts, through the reverse transcription polymerase chain reaction (RT-PCR). To date, no clear conclusions about an association between WT1 expression levels and APL have been reached. This patient successively received a combined treatment regimen consisting of hydroxycarbamide, arsenic trioxide and idarubicin plus cytarabine, which ultimately enabled complete remission. Unfortunately, he subsequently died of sudden massive hemoptysis because of pulmonary infection. CONCLUSION: Based on our findings and a review of the literature, abnormal functioning of WT1 may be a high-risk factor in cases of APL. Further studies aimed towards evaluating the impact of WT1 expression on the prognosis for APL patients are of interest.

摘要背景：急性早幼粒细胞白血病（Acute promyelocytic leukemia, APL）占急性髓系白血病（acute myeloid leukemia, AML）病例的8%~10%。高危型APL的缓解仍难以实现，且极易复发。
病例报告：本文报告1例外周血白细胞计数升高、骨髓呈现低颗粒变异形态的APL病例，该患者携带FMS样酪氨酸激酶3内部串联重复突变（fms-like tyrosine kinase-3 internal tandem duplication mutations, FLT3-ITD）以及PML-RARα的bcr-3亚型。尤为关键的是，通过逆转录聚合酶链反应（reverse transcription polymerase chain reaction, RT-PCR）检测，发现骨髓原始细胞中肾母细胞瘤基因（Wilms’ tumor gene, WT1）呈高表达状态。截至目前，学界关于WT1表达水平与APL之间的关联尚未达成明确结论。该患者先后接受羟基脲、三氧化二砷联合伊达比星+阿糖胞苷的联合治疗方案，最终实现完全缓解。不幸的是，患者后续因肺部感染引发大咯血，最终死亡。
结论：基于本研究结果并结合文献复习，WT1功能异常可能是APL的高危因素之一。未来开展旨在评估WT1表达对APL患者预后影响的相关研究具有重要意义。