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早幼粒细胞性急性白血病中 FLT3-ITD 状态与临床、细胞和分子特征的相关性。

Correlation between FLT3-ITD status and clinical, cellular and molecular profiles in promyelocytic acute leukemias.

机构信息

Laboratório BIOCOD Biotecnologia Ltda., Av. das Nações 2448, Portaria A, Vespasiano CEP 33200-000, MG, Brazil.

Hospital Santa Casa de Misericórdia de Belo Horizonte, Av. Francisco Sales 1111, Belo Horizonte CEP 30150-221, MG, Brazil.

出版信息

Leuk Res. 2015 Feb;39(2):131-7. doi: 10.1016/j.leukres.2014.11.010. Epub 2014 Nov 27.

Abstract

Internal tandem duplications (ITD) of FLT3 gene occur in about a third of acute promyelocytic leukemias (APL). We investigated the patterns of blood count, surface antigen, expression, chromosome aberrations, PML-RARa isoform, gene expression profile (GEP) and survival in 34 APL patients according to FLT3-ITD status. 97% had a t(15;17) and all of them carried PML-RARa gene fusion, 8 (23.5%) had a FLT3-ITD mutation. Presence of ITD was associated with higher Hb and WBC levels, bcr3 isoform, CD34 expression, CD2 or CD2/CD34 expression. In a multivariate analysis, Hb>9.6g/dL and WBC≥20 × 10(9)/L were important factors for predicting ITD presence. GEP showed that FLT3-ITD carriers clustered separately, even when as few as 5 genes were considered. This study provides further evidence that FLT3-ITDs carriers constitute a biologically distinct group of APL patients.

摘要

FLT3 基因内串联重复(ITD)发生在约三分之一的急性早幼粒细胞白血病(APL)中。我们根据 FLT3-ITD 状态研究了 34 例 APL 患者的血常规、表面抗原、表达、染色体异常、PML-RARa 异构体、基因表达谱(GEP)和生存模式。97%的患者存在 t(15;17),且均携带 PML-RARa 基因融合,8 例(23.5%)存在 FLT3-ITD 突变。存在 ITD 与更高的 Hb 和 WBC 水平、bcr3 异构体、CD34 表达、CD2 或 CD2/CD34 表达相关。多变量分析表明,Hb>9.6g/dL 和 WBC≥20×10(9)/L 是预测 ITD 存在的重要因素。GEP 显示,即使只考虑 5 个基因,FLT3-ITD 携带者也会聚类分开。本研究进一步证明,FLT3-ITD 携带者构成了一个生物学上不同的 APL 患者群体。

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