High expression of EVI1 and MEL1 is a compelling poor prognostic marker of pediatric AML
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 ~30% of patie...
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Published in | Leukemia Vol. 29; no. 5; pp. 1076 - 1083 |
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Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
01.05.2015
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | 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 ~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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0887-6924 1476-5551 |
DOI: | 10.1038/leu.2015.5 |