PMID- 17942707
OWN - NLM
STAT- MEDLINE
DCOM- 20080108
LR  - 20211020
IS  - 0890-9369 (Print)
IS  - 1549-5477 (Electronic)
IS  - 0890-9369 (Linking)
VI  - 21
IP  - 21
DP  - 2007 Nov 1
TI  - Meis1 is an essential and rate-limiting regulator of MLL leukemia stem cell 
      potential.
PG  - 2762-74
AB  - Oncogenic mutations of the MLL histone methyltransferase confer an unusual 
      ability to transform non-self-renewing myeloid progenitors into leukemia stem 
      cells (LSCs) by mechanisms that remain poorly defined. Misregulation of Hox genes 
      is likely to be critical for LSC induction and maintenance but alone it does not 
      recapitulate the phenotype and biology of MLL leukemias, which are clinically 
      heterogeneous--presumably reflecting differences in LSC biology and/or frequency. 
      TALE (three-amino-acid loop extension) class homeodomain proteins of the Pbx and 
      Meis families are also misexpressed in this context, and we thus employed 
      knockout, knockdown, and dominant-negative genetic techniques to investigate the 
      requirements and contributions of these factors in MLL oncoprotein-induced acute 
      myeloid leukemia. Our studies show that induction and maintenance of MLL 
      transformation requires Meis1 and is codependent on the redundant contributions 
      of Pbx2 and Pbx3. Meis1 in particular serves a major role in establishing LSC 
      potential, and determines LSC frequency by quantitatively regulating the extent 
      of self-renewal, differentiation arrest, and cycling, as well as the rate of in 
      vivo LSC generation from myeloid progenitors. Thus, TALE proteins are critical 
      downstream effectors within an essential homeoprotein network that serves a 
      rate-limiting regulatory role in MLL leukemogenesis.
FAU - Wong, Piu
AU  - Wong P
AD  - Department of Pathology, Stanford University School of Medicine, Stanford, 
      California 94305, USA.
FAU - Iwasaki, Masayuki
AU  - Iwasaki M
FAU - Somervaille, Tim C P
AU  - Somervaille TC
FAU - So, Chi Wai Eric
AU  - So CW
FAU - Cleary, Michael L
AU  - Cleary ML
LA  - eng
GR  - R01 CA055029/CA/NCI NIH HHS/United States
GR  - R37 CA042971/CA/NCI NIH HHS/United States
GR  - CA55029/CA/NCI NIH HHS/United States
GR  - CA42971/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20071017
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (MEIS1 protein, human)
RN  - 0 (Meis1 protein, mouse)
RN  - 0 (Myeloid Ecotropic Viral Integration Site 1 Protein)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Pbx2 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (Tgif1 protein, mouse)
RN  - 146150-81-4 (proto-oncogene protein Pbx3)
RN  - 149025-06-9 (Myeloid-Lymphoid Leukemia Protein)
SB  - IM
EIN - Genes Dev. 2007 Nov 15;21(22):3017. So, Chai Wai Eric [corrected to So, Chi Wai 
      Eric]
CIN - Genes Dev. 2007 Nov 15;21(22):2845-9. PMID: 18006680
MH  - Animals
MH  - *Cell Proliferation
MH  - Cell Transformation, Neoplastic/genetics
MH  - DNA-Binding Proteins/physiology
MH  - Gene Expression Regulation, Leukemic
MH  - Genes, cdc/physiology
MH  - Homeodomain Proteins/genetics/*physiology
MH  - Humans
MH  - K562 Cells
MH  - Leukemia, Myeloid, Acute/*genetics/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myeloid Ecotropic Viral Integration Site 1 Protein
MH  - Myeloid-Lymphoid Leukemia Protein/*genetics
MH  - Neoplasm Proteins/genetics/*physiology
MH  - Neoplasm Transplantation/mortality
MH  - Neoplastic Stem Cells/*cytology/pathology
MH  - Proto-Oncogene Proteins/genetics/physiology
MH  - Repressor Proteins/*physiology
MH  - Time Factors
MH  - Tumor Cells, Cultured
PMC - PMC2045130
EDAT- 2007/10/19 09:00
MHDA- 2008/01/09 09:00
PMCR- 2007/11/01
CRDT- 2007/10/19 09:00
PHST- 2007/10/19 09:00 [pubmed]
PHST- 2008/01/09 09:00 [medline]
PHST- 2007/10/19 09:00 [entrez]
PHST- 2007/11/01 00:00 [pmc-release]
AID - gad.1602107 [pii]
AID - 10.1101/gad.1602107 [doi]
PST - ppublish
SO  - Genes Dev. 2007 Nov 1;21(21):2762-74. doi: 10.1101/gad.1602107. Epub 2007 Oct 17.