Department of Pediatric Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, Maharashtra, India.
Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
Clin Lymphoma Myeloma Leuk. 2022 Apr;22(4):e221-e232. doi: 10.1016/j.clml.2021.09.020. Epub 2021 Oct 2.
Core binding factor acute myeloid leukemia (CBF-AML) belongs to favorable risk group in AML. However, approximately 50% of patients with CBF-AML remain incurable and their outcomes are also determined by the various co-occurring mutations. Though, FMS-like tyrosine kinase-3(FLT3) mutation in AML is associated with poor survival, the prevalence and prognostic significance of FLT3 mutations among CBF-AML is unknown.
We performed a systematic review and meta-analysis to assess the prevalence of FLT3 mutations (ITD and TKD) among patients with CBF-AML. The pooled prevalence of FLT3 mutations was estimated for patients with CBF-AML, t(8;21) and Inv(16). Pooled odds ratio was calculated to compare the prevalence of various FLT3 mutations within the 2 subsets of CBF-AML. A random effects model was adopted for analysis when heterogenicity existed (P< 0.05 or I > 50%). Otherwise, a fixed effects model was used.
The pooled prevalence of any FLT3 mutations among patients with CBF-AML was available from 18 studies and was 13% (95% CI: 10%-16%; I = 79%). Comparison of prevalence of FLT3 mutations between the 2 subgroups of CBF-AML showed that patients with t(8;21) had a higher prevalence of FLT3-ITD [pooled odds ratio(OR): 2.23 (95% CI:1.41-3.53, P < .01)] and lower prevalence of FLT3-TKD [pooled OR: 0.29 (95% CI:0.19-0.44; P < .01)] compared to patients with Inv(16). Additionally, we have discussed the prognostic significance of FLT3 mutations in CBF-AML patients.
The prevalence of FLT3-TKD mutation was commoner among Inv(16) AML while FLT3-ITD mutation was commoner among t(8;21) AML. Uniform reporting of outcomes is essential to understand the prognostic significance of FLT3 mutations among CBF-AML.
核心结合因子急性髓系白血病（CBF-AML）属于 AML 的低危组。然而，大约 50%的 CBF-AML 患者仍无法治愈，其预后也由各种共存突变决定。尽管 AML 中的 FMS 样酪氨酸激酶 3（FLT3）突变与不良生存相关，但 CBF-AML 中 FLT3 突变的流行率和预后意义尚不清楚。
我们进行了一项系统评价和荟萃分析，以评估 CBF-AML 患者中 FLT3 突变（ITD 和 TKD）的流行率。对于 CBF-AML、t（8；21）和 Inv（16）患者，我们估计了 FLT3 突变的总流行率。计算了合并优势比以比较 CBF-AML 两个亚组中各种 FLT3 突变的流行率。当存在异质性时（P<0.05 或 I>50%）采用随机效应模型进行分析。否则，使用固定效应模型。
共有 18 项研究提供了 CBF-AML 患者中任何 FLT3 突变的总流行率，为 13%（95%CI：10%-16%；I=79%）。比较 CBF-AML 两个亚组中 FLT3 突变的流行率发现，t（8；21）患者的 FLT3-ITD 发生率较高[合并优势比（OR）：2.23（95%CI：1.41-3.53，P<.01）]，FLT3-TKD 发生率较低[合并 OR：0.29（95%CI：0.19-0.44；P<.01）]。此外，我们还讨论了 FLT3 突变在 CBF-AML 患者中的预后意义。
FLT3-TKD 突变在 Inv（16）AML 中更为常见，而 FLT3-ITD 突变在 t（8；21）AML 中更为常见。统一报告结果对于了解 CBF-AML 中 FLT3 突变的预后意义至关重要。
