PRDM16表达在成人急性髓系白血病中的临床特征及预后影响
Clinical features and prognostic impact of PRDM16 expression in adult acute myeloid leukemia.
作者信息
Yamato Genki, Yamaguchi Hiroki, Handa Hiroshi, Shiba Norio, Kawamura Machiko, Wakita Satoshi, Inokuchi Koiti, Hara Yusuke, Ohki Kentaro, Okubo Jun, Park Myoung-Ja, Sotomatsu Manabu, Arakawa Hirokazu, Hayashi Yasuhide
机构信息
Department of Hematology/Oncology, Gunma Children's Medical Center, Gunma, Japan.
Department of Pediatrics, Gunma University Graduate School of Medicine, Gunma, Japan.
出版信息
Genes Chromosomes Cancer. 2017 Nov;56(11):800-809. doi: 10.1002/gcc.22483. Epub 2017 Aug 11.
High PRDM16 (also known as MEL1) expression is a representative marker of acute myeloid leukemia (AML) with NUP98-NSD1 and is a significant predictive marker for poor prognosis in pediatric AML. However, the clinical features of adult AML with PRDM16 expression remain unclear. PRDM16 is highly homologous to MDS1/EVI1, which is an alternatively spliced transcript of MECOM (also known as EVI1). We investigated PRDM16 expression in 151 AML patients, with 47 (31%) exhibiting high PRDM16 expression (PRDM16/ABL1 ratio ≥ 0.010). High PRDM16 expression significantly correlated with DNMT3A (43% vs. 15%, P < 0.001) and NPM1 (43% vs. 21%, P = 0.010) mutations and partial tandem duplication of KMT2A (22% vs. 1%, P < 0.001). Remarkably, high-PRDM16-expression patients were frequent in the noncomplete remission group (48% vs. 21%, P = 0.002). Overall survival (OS) was significantly worse in high-PRDM16-expression patients than in low-PRDM16-expression patients (5-year OS, 18% vs. 34%; P = 0.002). This trend was observed more clearly among patients aged <65 years (5-year OS, 21% vs. 50%; P = 0.001), particularly in FLT3-ITD-negative patients in the intermediate cytogenetic risk group (5-year OS, 25% vs. 59%; P = 0.009). These results suggest that high PRDM16 expression is a significant predictive marker for poor prognosis in adult AML patients, similar to pediatric AML patients.
高PRDM16（也称为MEL1）表达是伴有NUP98 - NSD1的急性髓系白血病（AML）的代表性标志物，并且是小儿AML预后不良的重要预测标志物。然而，具有PRDM16表达的成人AML的临床特征仍不清楚。PRDM16与MDS1/EVI1高度同源，MDS1/EVI1是MECOM（也称为EVI1）的可变剪接转录本。我们调查了151例AML患者的PRDM16表达情况，其中47例（31%）表现出高PRDM16表达（PRDM16/ABL1比值≥0.010）。高PRDM16表达与DNMT3A（43%对15%，P<0.001）和NPM1（43%对21%，P = 0.010）突变以及KMT2A的部分串联重复（22%对1%，P<0.001）显著相关。值得注意的是，高PRDM16表达患者在未完全缓解组中更为常见（48%对21%，P = 0.002）。高PRDM16表达患者的总生存期（OS）明显差于低PRDM16表达患者（五年OS，18%对34%；P = 0.002）。在年龄<65岁的患者中这种趋势更为明显（五年OS，21%对50%；P = 0.001），特别是在中等细胞遗传学风险组的FLT3 - ITD阴性患者中（五年OS，25%对59%；P = 0.009）。这些结果表明，高PRDM16表达与小儿AML患者类似，是成人AML患者预后不良的重要预测标志物。
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