PMID- 22828445
OWN - NLM
STAT- MEDLINE
DCOM- 20130228
LR  - 20171116
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Linking)
VI  - 27
IP  - 1
DP  - 2013 Jan
TI  - EVI-1 modulates leukemogenic potential and apoptosis sensitivity in human acute 
      lymphoblastic leukemia.
PG  - 56-65
LID - 10.1038/leu.2012.211 [doi]
AB  - The transcriptional regulator ecotropic viral integration site-1 (EVI-1) has 
      mainly been studied for its role in myeloid malignancies, in which high EVI-1 
      levels are associated with particularly aggressive disease. The role of EVI-1 in 
      lymphoid cells, however, is largely unknown. Here we show that EVI-1 is indeed 
      expressed in lymphoid malignancies such as acute lymphoblastic leukemia (ALL) and 
      a subset of chronic lymphocytic leukemia. Expression data from pediatric ALL 
      further suggest that high EVI-1 levels are associated with poor prognosis. 
      Suppression of EVI-1 expression by RNA interference reduces cell growth and 
      enhances apoptosis sensitivity in response to various stimuli in lymphoblastic 
      leukemia cells. At the molecular level, EVI-1 modulates expression of several 
      apoptosis-related genes (such as BCL2, BCL-x, XIAP, NOXA, PUMA, TRAIL-R1). 
      Furthermore, EVI-1 knockdown strongly impairs in vivo engraftment of 
      lymphoblastic leukemia cells upon transplantation in immune-permissive 
      NOD/SCID/IL2Rgamma(null) mice, conferring a survival benefit when compared with mice 
      transplanted with control cells. Thus, our data show that EVI-1 is expressed not 
      only in myeloid but also in lymphoid leukemias, and contributes to the 
      leukemogenic potential and apoptosis resistance of ALL cells.
FAU - Konantz, M
AU  - Konantz M
AD  - Department of Hematology and Oncology, University of Tuebingen Medical Center II, 
      Tuebingen, Germany.
FAU - Andre, M C
AU  - Andre MC
FAU - Ebinger, M
AU  - Ebinger M
FAU - Grauer, M
AU  - Grauer M
FAU - Wang, H
AU  - Wang H
FAU - Grzywna, S
AU  - Grzywna S
FAU - Rothfuss, O C
AU  - Rothfuss OC
FAU - Lehle, S
AU  - Lehle S
FAU - Kustikova, O S
AU  - Kustikova OS
FAU - Salih, H R
AU  - Salih HR
FAU - Handgretinger, R
AU  - Handgretinger R
FAU - Fend, F
AU  - Fend F
FAU - Baum, C
AU  - Baum C
FAU - Kanz, L
AU  - Kanz L
FAU - Quintanilla-Martinez, L
AU  - Quintanilla-Martinez L
FAU - Schulze-Osthoff, K
AU  - Schulze-Osthoff K
FAU - Essmann, F
AU  - Essmann F
FAU - Lengerke, C
AU  - Lengerke C
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120725
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Il2rg protein, mouse)
RN  - 0 (Interleukin Receptor Common gamma Subunit)
RN  - 0 (MDS1 and EVI1 Complex Locus Protein)
RN  - 0 (MECOM protein, human)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Adult
MH  - Animals
MH  - *Apoptosis
MH  - Blotting, Western
MH  - Case-Control Studies
MH  - Cell Cycle
MH  - Cell Proliferation
MH  - Child
MH  - DNA-Binding Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - Fluorescent Antibody Technique
MH  - Humans
MH  - Interleukin Receptor Common gamma Subunit/physiology
MH  - Leukemia, Lymphocytic, Chronic, B-Cell/genetics/metabolism/*pathology
MH  - Leukemia, Myeloid, Acute/genetics/metabolism/*pathology
MH  - MDS1 and EVI1 Complex Locus Protein
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics/metabolism/*pathology
MH  - Proto-Oncogenes/genetics
MH  - RNA, Small Interfering/genetics
MH  - Transcription Factors/antagonists & inhibitors/genetics/*metabolism
MH  - Tumor Cells, Cultured
EDAT- 2012/07/26 06:00
MHDA- 2013/03/01 06:00
CRDT- 2012/07/26 06:00
PHST- 2012/07/26 06:00 [entrez]
PHST- 2012/07/26 06:00 [pubmed]
PHST- 2013/03/01 06:00 [medline]
AID - leu2012211 [pii]
AID - 10.1038/leu.2012.211 [doi]
PST - ppublish
SO  - Leukemia. 2013 Jan;27(1):56-65. doi: 10.1038/leu.2012.211. Epub 2012 Jul 25.