Study of FLT3 Internal Tandem Duplication (FLT3-ITD) in Patients with Acute Promyelocytic Leukemia (APL).

Abstract

Objectives To evaluate the prevalence and association with clinical features of FLT3 internal tandem duplication (FLT3-ITD) in patients with newly-diagnosed acute promyelocytic leukemia (APL).Methods A total of 103 APL patients were screened by polymerase chain reaction (PCR) for FLT3-ITD.Results FLT3-ITD mutations were identified in 19.4% (20/103) patients. The FLT3-ITD was associated with short/variant form of PML-RARα isoforms (p<0.0001). Among 20 patients with FLT3-ITD, 16 patients presented with short, 2 with variant and 2 with long form of PML-RARα isoforms. The expression level of FLT3 via quantitative real-time RT-PCR was significantly increased in patients with FLT3-ITD (p<0.05). Patients with FLT3-ITD also presented significantly increased initial peripheral white blood cell (WBC) count (p<0.01), especially in patients with short/variant PML-RARα isoforms (p=0.015). For patients with long form PML-RARα, there was no significant difference in initial WBC count. For clinical outcome, 90% (18/20) of FLT3-ITD positive patients obtained complete remission and 16 evaluable patients (2 lost follow-up) remained in first remission with relatively short follow-up (median 26 months, 11-47), which was not significantly different from patients without FLT3-ITD.Conclusion FLT3-ITDs were frequently identified in patients with newly diagnosed APL. FLT3-ITD was associated with short/variant form of PML-RARα fusion gene and increased initial WBC. No significant impact of FLT3-ITD on treatment outcome was observed with limited follow-up.Association of FLT3-ITD and PML-RARα isoforms in patients with APLNoFLT3-ITD+FLT3-ITD−Long572(3.5%)55(96.5%)Short4116(39.0%)25(61.0%)Variant52(40%)3(60%)Total10320(19.4%)83(80.6%) [Display omitted] [Display omitted]