PMID- 20357826 OWN - NLM STAT- MEDLINE DCOM- 20100603 LR - 20211203 IS - 1476-5551 (Electronic) IS - 0887-6924 (Linking) VI - 24 IP - 5 DP - 2010 May TI - EVI1 overexpression in distinct subtypes of pediatric acute myeloid leukemia. PG - 942-9 LID - 10.1038/leu.2010.47 [doi] AB - Overexpression of the ecotropic virus integration-1 (EVI1) gene (EVI1+), localized at chromosome 3q26, is associated with adverse outcome in adult acute myeloid leukemia (AML). In pediatric AML, 3q26 abnormalities are rare, and the role of EVI1 is unknown. We studied 228 pediatric AML samples for EVI1+ using gene expression profiling and RQ-PCR. EVI1+ was found in 20/213 (9%) of children with de novo AML, and in 4/8 with secondary AML. It was predominantly found in MLL-rearranged AML (13/47), monosomy 7 (2/3), or FAB M6/7 (6/10), and mutually exclusive with core-binding factor AML, t(15;17), and NPM1 mutations. Fluorescent in situ hybridization (FISH) was performed to detect cryptic 3q26 abnormalities. However, none of the EVI1+ patients harbored structural 3q26 alterations. Although significant differences in 4 years pEFS for EVI1+ and EVI1- pediatric AML were observed (28%+/-11 vs 44%+/-4, P=0.04), multivariate analysis did not identify EVI1+ as an independent prognostic factor. We conclude that EVI1+ can be found in approximately 10% of pediatric AML. Although EVI1+ was not an independent prognostic factor, it was predominantly found in subtypes of pediatric AML that are related with an intermediate to unfavorable prognosis. Further research should explain the role of EVI1+ in disease biology in these cases. Remarkably, no 3q26 abnormalities were identified in EVI1+ pediatric AML. FAU - Balgobind, B V AU - Balgobind BV AD - Department of Pediatric Oncology/Hematology, Erasmus MC--Sophia Children's Hospital, Rotterdam, The Netherlands. FAU - Lugthart, S AU - Lugthart S FAU - Hollink, I H AU - Hollink IH FAU - Arentsen-Peters, S T J C M AU - Arentsen-Peters ST FAU - van Wering, E R AU - van Wering ER FAU - de Graaf, S S N AU - de Graaf SS FAU - Reinhardt, D AU - Reinhardt D FAU - Creutzig, U AU - Creutzig U FAU - Kaspers, G J L AU - Kaspers GJ FAU - de Bont, E S J M AU - de Bont ES FAU - Stary, J AU - Stary J FAU - Trka, J AU - Trka J FAU - Zimmermann, M AU - Zimmermann M FAU - Beverloo, H B AU - Beverloo HB FAU - Pieters, R AU - Pieters R FAU - Delwel, R AU - Delwel R FAU - Zwaan, C M AU - Zwaan CM FAU - van den Heuvel-Eibrink, M M AU - van den Heuvel-Eibrink MM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100401 PL - England TA - Leukemia JT - Leukemia JID - 8704895 RN - 0 (Biomarkers, Tumor) RN - 0 (DNA-Binding Proteins) RN - 0 (MDS1 and EVI1 Complex Locus Protein) RN - 0 (MECOM protein, human) RN - 0 (NPM1 protein, human) RN - 0 (RNA, Messenger) RN - 0 (Transcription Factors) RN - 117896-08-9 (Nucleophosmin) SB - IM MH - Biomarkers, Tumor/*genetics MH - Child MH - Child, Preschool MH - Chromosome Aberrations MH - Chromosomes, Human, Pair 3/*genetics MH - DNA-Binding Proteins/*genetics MH - Female MH - Gene Expression Profiling MH - *Gene Expression Regulation, Leukemic MH - Humans MH - In Situ Hybridization, Fluorescence MH - Leukemia, Myeloid, Acute/*genetics/metabolism MH - MDS1 and EVI1 Complex Locus Protein MH - Male MH - Nucleophosmin MH - Oligonucleotide Array Sequence Analysis MH - Prognosis MH - Proto-Oncogenes/*genetics MH - RNA, Messenger/genetics/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Survival Rate MH - Transcription Factors/*genetics EDAT- 2010/04/02 06:00 MHDA- 2010/06/04 06:00 CRDT- 2010/04/02 06:00 PHST- 2010/04/02 06:00 [entrez] PHST- 2010/04/02 06:00 [pubmed] PHST- 2010/06/04 06:00 [medline] AID - leu201047 [pii] AID - 10.1038/leu.2010.47 [doi] PST - ppublish SO - Leukemia. 2010 May;24(5):942-9. doi: 10.1038/leu.2010.47. Epub 2010 Apr 1.