PMID- 22553314
OWN - NLM
STAT- MEDLINE
DCOM- 20120824
LR  - 20211203
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 119
IP  - 24
DP  - 2012 Jun 14
TI  - EVI1 is critical for the pathogenesis of a subset of MLL-AF9-rearranged AMLs.
PG  - 5838-49
LID - 10.1182/blood-2011-11-393827 [doi]
AB  - The proto-oncogene EVI1 (ecotropic viral integration site-1), located on 
      chromosome band 3q26, is aberrantly expressed in human acute myeloid leukemia 
      (AML) with 3q26 rearrangements. In the current study, we showed, in a large AML 
      cohort carrying 11q23 translocations, that  approximately  43% of all mixed lineage leukemia 
      (MLL)-rearranged leukemias are EVI1(pos). High EVI1 expression occurs in AMLs 
      expressing the MLL-AF6, -AF9, -AF10, -ENL, or -ELL fusion genes. In addition, we 
      present evidence that EVI1(pos) MLL-rearranged AMLs differ molecularly, 
      morphologically, and immunophenotypically from EVI1(neg) MLL-rearranged 
      leukemias. In mouse bone marrow cells transduced with MLL-AF9, we show that 
      MLL-AF9 fusion protein maintains Evi1 expression on transformation of Evi1(pos) 
      HSCs. MLL-AF9 does not activate Evi1 expression in MLL-AF9-transformed 
      granulocyte macrophage progenitors (GMPs) that were initially Evi1(neg). 
      Moreover, shRNA-mediated knockdown of Evi1 in an Evi1(pos) MLL-AF9 mouse model 
      inhibits leukemia growth both in vitro and in vivo, suggesting that Evi1 provides 
      a growth-promoting signal. Using the Evi1(pos) MLL-AF9 mouse leukemia model, we 
      demonstrate increased sensitivity to chemotherapeutic agents on reduction of Evi1 
      expression. We conclude that EVI1 is a critical player in tumor growth in a 
      subset of MLL-rearranged AMLs.
FAU - Bindels, Eric M J
AU  - Bindels EM
AD  - Department of Hematology, Erasmus University Medical Center, Rotterdam, The 
      Netherlands.
FAU - Havermans, Marije
AU  - Havermans M
FAU - Lugthart, Sanne
AU  - Lugthart S
FAU - Erpelinck, Claudia
AU  - Erpelinck C
FAU - Wocjtowicz, Elizabeth
AU  - Wocjtowicz E
FAU - Krivtsov, Andrei V
AU  - Krivtsov AV
FAU - Rombouts, Elwin
AU  - Rombouts E
FAU - Armstrong, Scott A
AU  - Armstrong SA
FAU - Taskesen, Erdogan
AU  - Taskesen E
FAU - Haanstra, Jurgen R
AU  - Haanstra JR
FAU - Beverloo, H Berna
AU  - Beverloo HB
FAU - Dohner, Hartmut
AU  - Dohner H
FAU - Hudson, Wendy A
AU  - Hudson WA
FAU - Kersey, John H
AU  - Kersey JH
FAU - Delwel, Ruud
AU  - Delwel R
FAU - Kumar, Ashish R
AU  - Kumar AR
LA  - eng
GR  - K08 CA122191/CA/NCI NIH HHS/United States
GR  - R01 CA087053/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120502
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Histones)
RN  - 0 (MAS1 protein, human)
RN  - 0 (MDS1 and EVI1 Complex Locus Protein)
RN  - 0 (MECOM protein, human)
RN  - 0 (MLL-AF9 fusion protein, human)
RN  - 0 (Mecom protein, mouse)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Proto-Oncogene Mas)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 149025-06-9 (Myeloid-Lymphoid Leukemia Protein)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Animals
MH  - Bone Marrow Cells/metabolism/pathology
MH  - Cell Proliferation
MH  - Cell Transformation, Neoplastic/genetics
MH  - Chromosomes, Human, Pair 11/genetics
MH  - Colony-Forming Units Assay
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Leukemic
MH  - Gene Knockdown Techniques
MH  - Gene Rearrangement/*genetics
MH  - Histones/metabolism
MH  - Humans
MH  - Leukemia, Myeloid, Acute/*classification/etiology/*genetics
MH  - Lysine/metabolism
MH  - MDS1 and EVI1 Complex Locus Protein
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myeloid-Lymphoid Leukemia Protein/*genetics
MH  - Oncogene Proteins, Fusion/*genetics
MH  - Promoter Regions, Genetic/genetics
MH  - Proto-Oncogene Mas
MH  - Proto-Oncogenes/genetics
MH  - RNA, Messenger/genetics/metabolism
MH  - Transcription Factors/genetics/*metabolism
PMC - PMC3382941
EDAT- 2012/05/04 06:00
MHDA- 2012/08/25 06:00
PMCR- 2013/06/14
CRDT- 2012/05/04 06:00
PHST- 2012/05/04 06:00 [entrez]
PHST- 2012/05/04 06:00 [pubmed]
PHST- 2012/08/25 06:00 [medline]
PHST- 2013/06/14 00:00 [pmc-release]
AID - S0006-4971(20)47701-8 [pii]
AID - 2011/393827 [pii]
AID - 10.1182/blood-2011-11-393827 [doi]
PST - ppublish
SO  - Blood. 2012 Jun 14;119(24):5838-49. doi: 10.1182/blood-2011-11-393827. Epub 2012 
      May 2.