Adnan-Awad Shady, Gaber Ola, Eltokhy Soad A, Mourad Dalia, Amer Mariam, Kandeel Eman Z, Eldesouky Ihab
Clin Lab. 2017 May 1;63(5):1027-1034. doi: 10.7754/Clin.Lab.2017.170121.
FLT3-ITD mutations are common in AML subgroups, particularly in Acute Promyelocytic Leukemia (APL). It infers poor prognosis in AML patients; however, its prognostic value in APL is still controversial. We aimed to assess the distribution and prognostic value of FLT3-ITD mutation within AML subgroups, focusing on APL.
In NCI, Cairo University, 346 newly diagnosed AML patients were included. Morphological, immunophenotypic and cytogenetic analysis were done at presentation and fixed follow-up points with monitoring in follow up visits of patients. FLT3-ITD mutations were detected using RT-PCR.
FLT3-ITD mutations were detected in 18.5% of AML patients with significant higher incidence in M3 patients (35.5%, p = 0.027) in comparison to other types. There was significant negative association between FLT3ITD mutations and CD34 expression (p = 0.026). FLT3 wild patients had a significantly better response on Day 35 than the mutant group (p = 0.046). Overall Survival (OS) of the wild group was significantly better than that of the mutant group (p = 0.003). In APL patients, OS of wild-FLT3 patients was significantly better than of those with mutant FLT3 (p = 0.018). In non-APL patients, favorable cytogenetic changes - t(8;21) and inv(16) - are more common in FLT3 wild group (12.8%) than in FLT3 mutant group (6.3%). In non-APL patients, FLT3-ITD mutation retained its adverse prognostic effect (p = 0.016). CD34 expression affected survival in both FLT3 mutant and wild groups.
We conclude that FLT3-ITD mutations infer poor prognostic effects both in AML patients generally and in the APL group specifically. CD34 may have a prognostic impact in FLT3-ITD mutant patients, which is to be further investigated.
FLT3-ITD突变在急性髓系白血病（AML）亚组中很常见，尤其是在急性早幼粒细胞白血病（APL）中。它提示AML患者预后不良；然而，其在APL中的预后价值仍存在争议。我们旨在评估FLT3-ITD突变在AML亚组中的分布及预后价值，重点关注APL。
纳入开罗大学美国国立癌症研究所的346例新诊断的AML患者。在初诊时以及固定的随访时间点进行形态学、免疫表型和细胞遗传学分析，并在患者随访期间进行监测。使用逆转录聚合酶链反应（RT-PCR）检测FLT3-ITD突变。
18.5%的AML患者检测到FLT3-ITD突变，M3患者的发生率显著更高（35.5%，p = 0.027），与其他类型相比。FLT3-ITD突变与CD34表达之间存在显著负相关（p = 0.026）。FLT3野生型患者在第35天的反应明显优于突变组（p = 0.046）。野生组的总生存期（OS）明显优于突变组（p = 0.003）。在APL患者中，FLT3野生型患者的OS明显优于FLT3突变型患者（p = 0.018）。在非APL患者中，有利的细胞遗传学改变——t(8;21)和inv(16)——在FLT3野生组（12.8%）中比在FLT3突变组（6.3%）中更常见。在非APL患者中，FLT3-ITD突变保留了其不良预后作用（p = 0.016）。CD34表达影响FLT3突变型和野生型组的生存。
我们得出结论，FLT3-ITD突变在AML患者总体以及APL组中均提示不良预后作用。CD34可能对FLT3-ITD突变患者有预后影响，这有待进一步研究。
