High expression of EVI1 and MEL1 is a compelling poor prognostic marker of pediatric AML

被引：45

作者：

Jo, A. ^{[1
]}

Mitani, S. ^{[1
]}

Shiba, N. ^{[2
,3
]}

Hayashi, Y. ^{[2
]}

Hara, Y. ^{[2
,3
]}

Takahashi, H. ^{[4
]}

Tsukimoto, I. ^{[5
]}

Tawa, A. ^{[6
]}

Horibe, K. ^{[7
]}

Tomizawa, D. ^{[8
]}

Taga, T. ^{[9
]}

Adachi, S. ^{[10
]}

Yoshida, T. ^{[1
]}

Ichikawa, H. ^{[1
,11
,12
]}

机构：

[1] Natl Canc Ctr, Div Genet, Tokyo 1040045, Japan

[2] Gunma Childrens Med Ctr, Dept Hematol Oncol, Shibukawa, Japan

[3] Gunma Univ, Grad Sch Med, Dept Pediat, Maebashi, Gunma 371, Japan

[4] Chiba Univ, Grad Sch Hort, Matsudo, Chiba, Japan

[5] Toho Univ, Sch Med, Dept Pediat 1, Tokyo, Japan

[6] Osaka Natl Hosp, Natl Hosp Org, Dept Pediat, Osaka, Japan

[7] Natl Hosp Org, Nagoya Med Ctr, Clin Res Ctr, Nagoya, Aichi, Japan

[8] Tokyo Med & Dent Univ, Dept Pediat, Tokyo, Japan

[9] Shiga Univ Med Sci, Dept Pediat, Otsu, Shiga 52021, Japan

[10] Kyoto Univ, Human Hlth Sci, Kyoto, Japan

[11] Natl Canc Ctr, Res Inst, Dept Clin Genom, Tokyo 104, Japan

[12] Natl Canc Ctr, Exploratory Oncol Res & Clin Trial Ctr, Div Translat Res, Tokyo 104, Japan

来源：

LEUKEMIA | 2015年 / 29卷 / 05期

关键词：

ACUTE MYELOID-LEUKEMIA; POLYMERASE-CHAIN-REACTION; GENE-EXPRESSION; TRANSLOCATIONS; CYTARABINE; SIGNATURE; PREDICTION; CHILDREN; SUBTYPES; THERAPY;

D O I：

10.1038/leu.2015.5

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

EVI1 and MEL1 are homolog genes whose transcriptional activations by chromosomal translocations are known in small subsets of leukemia. From gene expression profiling data of 130 Japanese pediatric acute myeloid leukemia (AML) patients, we found that EVI1 and MEL1 were overexpressed in similar to 30% of patients without obvious translocations of these gene loci, and that their high expression was significantly associated with inferior survival. High EVI1 expression was detected mainly in myelomonocytic-lineage (designated as e-M4/M5 subtype) leukemia with MLL rearrangements and in megakaryocytic-lineage (designated as e-M7 subtype) leukemia, and its prognostic association was observed in the e-M4/M5 subtype but not in the e-M7 subtype. On the other hand, high MEL1 expression was detected in myelocytic-lineage (designated as e-M0/M1/M2 subtype) and e-M4/M5 subtype leukemia without MLL rearrangements, and its prognostic association was independent from the subtypes. Because of their subtype-dependent and mutually exclusive expression, a combined evaluation of their high expression enabled a clear distinction of patients with inferior survival (P < 0.00001 in event-free survival (EFS) and overall survival (OS)). This association was confirmed by quantitative reverse transcription PCR analysis of an independent cohort of 81 patients (P = 0.00017 in EFS, P = 0.00028 in OS). We propose that the combined estimation of EVI1 and MEL1 expression will be an effective method to predict the prognosis of pediatric AML.

引用

页码：1076 / 1083

页数：8

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