PMID- 10979955
OWN - NLM
STAT- MEDLINE
DCOM- 20001004
LR  - 20220224
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 96
IP  - 6
DP  - 2000 Sep 15
TI  - Analysis of the role of AML1-ETO in leukemogenesis, using an inducible transgenic 
      mouse model.
PG  - 2108-15
AB  - As reported previously, AML1-ETO knock-in mice were generated to investigate the 
      role of AML1-ETO in leukemogenesis and to mimic the progression of t(8;21) 
      leukemia. These knock-in mice died in midgestation because of hemorrhaging in the 
      central nervous system and a block of definitive hematopoiesis during 
      embryogenesis. Therefore, they are not a good model system for the development of 
      acute myeloid leukemia. Therefore, mice were generated in which the expression of 
      AML1-ETO is under the control of a tetracycline-inducible system. Multiple lines 
      of transgenic mice have been produced with the AML1-ETO complementary DNA 
      controlled by a tetracycline-responsive element. In the absence of the antibiotic 
      tetracycline, AML1-ETO is strongly expressed in the bone marrow of AML1-ETO and 
      tet-controlled transcriptional activator double-positive transgenic mice. 
      Furthermore, the addition of tetracycline reduces AML1-ETO expression in 
      double-positive mice to nondetectable levels. Throughout the normal murine 
      lifespan of 24 months, mice expressing AML1-ETO have not developed leukemia. In 
      spite of this, abnormal maturation and proliferation of progenitor cells have 
      been observed from these animals. These results demonstrate that AML1-ETO has a 
      very restricted capacity to transform cells. Either the introduction of 
      additional genetic changes or the expression of AML1-ETO at a particular stage of 
      hematopoietic cell differentiation will be necessary to develop a model for 
      studying the pathogenesis of t(8;21).
FAU - Rhoades, K L
AU  - Rhoades KL
AD  - Department of Molecular and Experimental Medicine, The Scripps Research 
      Institute, La Jolla, CA 92037, USA.
FAU - Hetherington, C J
AU  - Hetherington CJ
FAU - Harakawa, N
AU  - Harakawa N
FAU - Yergeau, D A
AU  - Yergeau DA
FAU - Zhou, L
AU  - Zhou L
FAU - Liu, L Q
AU  - Liu LQ
FAU - Little, M T
AU  - Little MT
FAU - Tenen, D G
AU  - Tenen DG
FAU - Zhang, D E
AU  - Zhang DE
LA  - eng
GR  - CA72009/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (AML1-ETO fusion protein, human)
RN  - 0 (Core Binding Factor Alpha 2 Subunit)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RUNX1 Translocation Partner 1 Protein)
RN  - 0 (Runx1 protein, mouse)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Acute Disease
MH  - Animals
MH  - Core Binding Factor Alpha 2 Subunit
MH  - DNA-Binding Proteins/genetics
MH  - *Gene Expression Regulation, Neoplastic
MH  - Genetic Predisposition to Disease
MH  - Leukemia, Myeloid/*etiology/*genetics
MH  - Mice
MH  - Mice, Transgenic
MH  - Oncogene Proteins, Fusion/*genetics
MH  - *Proto-Oncogene Proteins
MH  - RUNX1 Translocation Partner 1 Protein
MH  - Transcription Factors/*genetics
EDAT- 2000/09/09 11:00
MHDA- 2000/10/07 11:01
CRDT- 2000/09/09 11:00
PHST- 2000/09/09 11:00 [pubmed]
PHST- 2000/10/07 11:01 [medline]
PHST- 2000/09/09 11:00 [entrez]
AID - S0006-4971(20)54398-X [pii]
PST - ppublish
SO  - Blood. 2000 Sep 15;96(6):2108-15.